bluuebunny/crossref_metadata_2025 huggingface dataset:
Dual-reflector configuration in varied line-space grating displacement sensor
Authors: Liu Zhengkun , Xu Xiangdong , Zhou Qin , Liu Bin , Fu Shaojun
Published: April 2008

A method to improve the accuracy of the wavelength encoding varied line-space grating displacement sensor is presented. Based on the detailed analysis of the measured displacement errors from the single-mirror configuration sensor, a dual-reflector configuration is used to replace the previous configuration, and greatly decreases its errors. Experiments are conducted in order to make comparison of the two configurations. The results show that the measured displacement error of the sensor with dual-reflector configuration is lower than 0.03mm in full scale (0to50mm), only about 10% of the sensor with single-mirror configuration.
Ab initio investigation of the electronic structure and bonding of BH, BH−, and HBBH molecules
Authors: Miliordos Evangelos , Mavridis Aristides
Published: April 2008

By correlating all electrons and employing core-tuned correlation consistent basis sets of quintuple-ζ quality, we applied multireference and coupled-cluster methods to study 32 electronic states of the diatomic BH molecule, two bound states of BH−, and three states of the linear HBBH molecule. We have constructed full potential energy curves and profiles, reporting binding energies, geometries, spectroscopic parameters, dipole moments, and energy separations, whereas our numerical results are in excellent agreement with available experimental numbers. We are trying as well to interpret the binding modes of a large number of the examined states. 18 states of BH are of Rydberg character, with the BH− anion revealing similar structural characteristics to the isoelectronic CH species. The first three states of HBBH X̃Σg−3, ãΔg1, and b̃Σg+1 diabatically correlate to two aΠ3 BH fragments, they are similar to the states bΣg−3, BΔg1, and B′Σg+1 of the isoelectronic molecule C2, however, their ordering follows that of the first three states of the O2 molecule.
The role of the excited electronic states in the C++H2O reaction
Authors: Flores Jesús R. , González Adán B.
Published: April 2008

The electronic excited states of the [COH2]+ system have been studied in order to establish their role in the dynamics of the C++H2O→[COH]++H reaction, which is a prototypical ion-molecule reaction. The most relevant minima and saddle points of the lowest excited state have been determined and energy profiles for the lowest excited doublet and quartet electronic states have been computed along the fragmentation and isomerization coordinates. Also, nonadiabatic coupling strengths between the ground and the first excited state have been computed where they can be large. Our analysis suggests that the first excited state could play an important role in the generation of the formyl isomer, which has been detected in crossed beam experiments [D. M. Sonnenfroh et al., J. Chem. Phys. 83, 3985 (1985)], but could not be explained in quasiclassical trajectory computations [Y. Ishikawa et al., Chem. Phys. Lett. 370, 490 (2003); J. R. Flores, J. Chem. Phys. 125, 164309 (2006)].
Shock compression of condensed matter using multimaterial reactive ghost fluid method
Authors: Kim Ki-hong , Yoh Jack J.
Published: April 2008

For the flow analysis of reactive compressible media involving energetic materials and deforming metallic boundaries, a HYDRO-SCCM (shock compression of condensed matter) tool is developed for handling multiphysics shock analysis of energetic and inert matters. The highly energetic flows give rise to the strong nonlinear shock waves and the high strain rate deformation of solid boundaries at high pressure and temperature. For handling the large gradients associated with these complex flows in the condensed phase as well as in the reactive gaseous phase, a new Eulerian multifluid method is formulated. The numerical methodology is described in this paper, while the extended applications and the capacity of the tool are discussed in a separate paper [J. J. Yoh and K. H. Kim, “Shock Compression of Condensed Matter using Eulerian Multimaterial Method: Applications to multi-dimensional shocks, deflagration, detonation, and laser ablation,” J. Appl. Phys. (accepted)].
Remarks on nonlinear Schrödinger equation with harmonic potential
Authors: Xu Runzhang , Liu Yacheng
Published: April 2008

We study the Cauchy problem of nonlinear Schrödinger equation with harmonic potential. Some self-contradictory assumptions and some problems [J. Shu and J. Zhang, J. Math. Phys. 47, 063503 (2006)] are pointed out and corrected. And some relative results are improved.
Scaling law of stable single cells in density fingering of chemical fronts
Authors: Tóth Tamara , Horváth Dezsö , Tóth Ágota
Published: April 2008

Stable single fingers evolving in a thin layer of hydrodynamically unstable reactive solution are investigated in moderately wide Hele–Shaw cells. The mixing length associated with the final pattern is shown to be proportional to the width of the container. The scaling law, which is best illustrated by the overlay of temporal average front profiles, is demonstrated for two chemical compositions and boundaries of different thermal conductances. The observed single finger is found to be independent of the orientation of the reaction vessel for a wide range of tilt angles.
Floating electrode optoelectronic tweezers: Light-driven dielectrophoretic droplet manipulation in electrically insulating oil medium
Authors: Park Sungyong , Pan Chenlu , Wu Ting-Hsiang , Kloss Christoph , Kalim Sheraz , Callahan Caitlin E. , Teitell Michael , Chiou Eric P. Y.
Published: April 2008

We report an optical actuation mechanism, floating electrode optoelectronic tweezers (FEOET). FEOET enables light-driven transport of aqueous droplets immersed in electrically insulating oil on a featureless photoconductive glass layer with direct optical images. We demonstrate that a 681μm de-ionized water droplet immersed in corn oil medium is actuated by a 3.21μW laser beam with an average intensity as low as 4.08μW∕mm2 at a maximum speed of 85.1μm∕s on a FEOET device. FEOET provides a promising platform for massively parallel droplet manipulation with optical images on low cost, silicon-coated glass. The FEOET device structure, fabrication, working principle, numerical simulations, and operational results are presented in this letter.
Optically induced long-lived electron spin coherence in ZnSe∕BeTe type-II quantum wells
Authors: Mino H. , Kouno Y. , Oto K. , Muro K. , Akimoto R. , Takeyama S.
Published: April 2008

The spin coherence of photoexcited electrons in ZnSe∕BeTe type-II quantum wells has been investigated by the time-resolved Kerr rotation technique. Fast and efficient escape of photoexcited holes from the ZnSe layers to the BeTe layers suppresses the electron-hole recombination and their exchange interaction. This effect leads to the formation of dense electrons in ZnSe layers and long electron spin dephasing time reaching a value of 6.1ns at 1.4K.
Wide band resonant ultrasound spectroscopy of spheroidal modes for high accuracy estimation of Poisson coefficient of balls
Authors: Deneuville François , Duquennoy Marc , Ouaftouh Mohammadi , Jenot Frédéric , Ourak Mohamed , Desvaux Sébastien
Published: April 2008

An original inversion method specifically adapted to the estimation of Poisson coefficient of balls by using their resonance spectra is described. From the study of their elastic vibrations, it is possible to accurately characterize the balls. The proposed methodology can create both spheroidal modes in the balls and detect such vibrations over a large frequency range. Experimentally, by using both an ultrasonic probe for the emission (piezoelectric transducer) and a heterodyne optic probe for the reception (interferometer), it was possible to take spectroscopic measurements of spheroidal vibrations over a large frequency range (100kHz–45MHz) in a continuous regime. This method, which uses ratios between wave resonance frequencies, allows the Poisson coefficient to be determined independently of Young’s modulus and the ball’s radius and density. This has the advantage of providing highly accurate estimations of Poisson coefficient (±4.3×10−4) over a wide frequency range.
Sb-doped p-ZnO∕Ga-doped n-ZnO homojunction ultraviolet light emitting diodes
Authors: Chu S. , Lim J. H. , Mandalapu L. J. , Yang Z. , Li L. , Liu J. L.
Published: April 2008

ZnO p-n homojunction light emitting diodes were fabricated based on p-type Sb-doped ZnO∕n-type Ga-doped ZnO thin films. Low resistivity Au∕NiO and Au∕Ti contacts were formed on top of p-type and n-type ZnO layers, respectively. Au∕NiO contacts on p-type ZnO exhibited a low specific resistivity of 7.4×10−4Ωcm2. The light emitting diodes yielded strong near-band-edge emissions in temperature-dependent and injection current-dependent electroluminescence measurements.
Physics of enhanced impact ionization in strained-Si p-channel metal-oxide-semiconductor field-effect transistors
Authors: Kang Ting-Kuo
Published: April 2008

This paper investigates the impact ionization phenomenon in strained-Si p-channel metal-oxide-semiconductor field-effect transistors with different strained-Si cap layer thicknesses at a Ge content of 20%. From the relationship between the impact ionization efficiency and the electric field in the pinch-off region, the strain-induced enhancement of the impact ionization efficiency appears to be quite consistent despite the high hole mobility and considerable scattering in the strained-Si cap layer; this consistent enhancement can be attributed to a decrease in the bandgap energy, regardless of the modification of the mean free path of the holes.
When Good Smells Go Bad: A Sociohistorical Understanding of Agricultural Odor Pollution
Authors: Carolan Michael S
Published: April 2008

In this paper, I seek to add to the sociological and geographical literature on odor by documenting the processes through which perceptions of agricultural odors are mediated and contested. Specifically, its empirical focus is on how residents living near a large-scale hog facility within the state of Iowa actively ‘do’ smell. In doing this, this papers draws not only from the historical, anthropological, and sociological literature on odor, but also from the field of animal (rural) geography. The findings of this research are organized around the following themes: (1) rural–urban transgressions; (2) inside–outside policing; (3) ties to local social network; (4) perceptions of agriculture; (5) a sense of powerlessness; and (6) shaping smell through sight. When taken together, an understanding of agricultural odor is provided that is both active (in that it is something we ‘do’) and historical (recognizing that such ‘doing’ always occurs within a particular sociohistorical milieu).
Dephosphorylation of 2,3-bisphosphoglycerate by MIPP expands the regulatory capacity of the Rapoport–Luebering glycolytic shunt
Authors: Cho Jaiesoon , King Jason S. , Qian Xun , Harwood Adrian J. , Shears Stephen B.
Published: April 2008

The Rapoport–Luebering glycolytic bypass comprises evolutionarily conserved reactions that generate and dephosphorylate 2,3-bisphosphoglycerate (2,3-BPG). For >30 years, these reactions have been considered the responsibility of a single enzyme, the 2,3-BPG synthase/2-phosphatase (BPGM). Here, we show that
Dictyostelium
, birds, and mammals contain an additional 2,3-BPG phosphatase that, unlike BPGM, removes the 3-phosphate. This discovery reveals that the glycolytic pathway can bypass the formation of 3-phosphoglycerate, which is a precursor for serine biosynthesis and an activator of AMP-activated protein kinase. Our 2,3-BPG phosphatase activity is encoded by the previously identified gene for multiple inositol polyphosphate phosphatase (MIPP1), which we now show to have dual substrate specificity. By genetically manipulating Mipp1 expression in
Dictyostelium
, we demonstrated that this enzyme provides physiologically relevant regulation of cellular 2,3-BPG content. Mammalian erythrocytes possess the highest content of 2,3-BPG, which controls oxygen binding to hemoglobin. We determined that total MIPP1 activity in erythrocytes at 37°C is 0.6 mmol 2,3-BPG hydrolyzed per liter of cells per h, matching previously published estimates of the phosphatase activity of BPGM. MIPP1 is active at 4°C, revealing a clinically significant contribution to 2,3-BPG loss during the storage of erythrocytes for transfusion. Hydrolysis of 2,3-BPG by human MIPP1 is sensitive to physiologic alkalosis; activity decreases 50% when pH rises from 7.0 to 7.4. This phenomenon provides a homeostatic mechanism for elevating 2,3-BPG levels, thereby enhancing oxygen release to tissues. Our data indicate greater biological significance of the Rapoport–Luebering shunt than previously considered.
Feeling affect in a second language
Authors: Segalowitz Norman , Trofimovich Pavel , Gatbonton Elizabeth , Sokolovskaya Anna
Published: April 2008

Anecdotal evidence from second language users and results from experimental studies indicate that affectively valent words are not always represented identically in a person’s first language (L1) and second language (L2) mental lexicons. The present study investigated whether such differences reflect how automatic (immediate, involuntary) the processing is of the affective element of affectively valent words, and what the relation is between this kind of processing and general word recognition efficiency for L2 words lacking affective valency. Participants were 48 L1 speakers of English with L2 French. Automaticity of processing adjectives with affective valence was operationalized using an Implicit Affect Association Task (IAAT) developed for this purpose. General efficiency in L2 word recognition was operationalized using a speeded semantic classification task with affectively neutral concrete nouns. Reaction time results from the IAAT showed that the processing of affectively valent words was less automatic in the L2 than in the L1. However, results from the semantic classification task indicated that this effect is not related to general weaker L2 word recognition abilities. Implications for an understanding of the L2 mental lexicon are discussed.
Structural and conceptual equivalence in the acquisition and use of emotion words in a second language
Authors: Pavlenko Aneta
Published: April 2008

The purpose of the study presented here is to examine the importance of structural and conceptual (non-)equivalence in the acquisition and use of emotion words in a second language (L2). The use of these words is examined in a corpus of 206 narratives collected with two stimuli from first language (L1) speakers of Russian and English, and L2 learners of Russian and English. The results of the quantitative and qualitative analyses of lexical choices made by the participants show that in the case of structural non-equivalence L2 learners can shift patterns of structural selection in the mental lexicon. Thus, L2 learners of English pattern with L1 English speakers in favoring adjectival constructions in the same context where L1 and L2 Russian speakers favor verbs. Conceptual non-equivalence, on the other hand, was shown to complicate acquisition of emotion words and lead to negative transfer, lexical borrowing, and avoidance. Implications are offered for models of the bilingual mental lexicon and for L2 instruction.
Perceiving and responding to embarrassing predicaments across languages
Authors: Vaid Jyotsna , Choi Hyun , Chen Hsin-Chin , Friedman Mike
Published: April 2008

The experience of embarrassment was explored in two experiments comparing monolingual and bilingual speakers from cultures varying in the degree of elaboration of the embarrassment lexicon. In Experiment 1, narratives in English or Korean depicting three types of embarrassing predicaments were to be rated on their embarrassability and humorousness by Korean-English bilinguals, Korean monolinguals, and Euro-American monolinguals. All groups judged certain predicaments (involving social gaffes) to be the most embarrassing. However, significant group and language differences occurred in judgments of the intensity of embarrassment and amusement judgments evoked. Euro-Americans exhibited higher overall levels of amusement than the two Korean groups who, in turn, reported higher levels of embarrassment, particularly for certain predicament types and contexts (ingroup members present). Further, for the bilinguals, inept performance predicaments in English were judged more embarrassing than those in Korean, whereas all predicament types were judged more amusing when framed with English emotion labels. Bilinguals also appeared to show a heightened embarrassability relative to both monolingual groups. Experiment 2 found lexical selection differences in open-ended responses to embarrassing predicaments depicted in each language, with Euro-Americans preferring to give justifications or use humor to minimize the embarrassment and Korean-English bilinguals preferring to give apologies or say nothing. The findings are interpreted to reflect the influence of culturally-mediated schemas guiding the activation and processing of emotion vocabulary.
Pius XII: romanità, prophesy and charisma
Authors: Logan Oliver
Published: April 2008

The modern popular cult of the Pope, which originated with the ‘disinherited’ papacy of Pius IX, reached its acme with Pius XII. Phases of intensification of this cult, which was linked to other ‘devotions’, those of the Sacred Heart of Jesus and of the Virgin Mary, served to mobilize the Catholic masses at critical junctures for the Catholic Church and in the face of what were perceived as political threats. Pius XII had to animate ‘movement’ in an age proclaimed to be one of a unique crisis of civilization. The projection of him as a charismatic figure was linked to that of Rome as a sacred centre and as the very fulcrum of world history. The Catholic activist ethos of ‘movement’ and also the presentation of the interchange between Pius XII and the Crowd had features in common with Fascist rhetorics, but ultimately the cult of the ‘victim-Pope’ represented an inversion of the crasser forms of power-imagery.
Cell polarization during monopolar cytokinesis
Authors: Hu Chi-Kuo , Coughlin Margaret , Field Christine M. , Mitchison Timothy J.
Published: April 2008

During cytokinesis, a specialized set of proteins is recruited to the equatorial region between spindle poles by microtubules and actin filaments, enabling furrow assembly and ingression before cell division. We investigate the mechanisms underlying regional specialization of the cytoskeleton in HeLa cells undergoing drug-synchronized monopolar cytokinesis. After forced mitotic exit, the cytoskeleton of monopolar mitotic cells is initially radially symmetric but undergoes a symmetry-breaking reaction that simultaneously polarizes microtubules and the cell cortex, with a concentration of cortical furrow markers into a cap at one side of the cell. Polarization requires microtubules, F-actin, RhoA, Myosin II activity, and Aurora B kinase activity. Aurora B localizes to actin cables in a gap between the monopolar midzone and the furrow-like cortex, suggesting a communication between them. We propose that feedback loops between cortical furrow components and microtubules promote symmetry breaking during monopolar cytokinesis and regional specialization of the cytoskeleton during normal bipolar cytokinesis.
Opposing effects of interferon‐α and interferon‐γ on the expression of major histocompatibility complex class I chain‐related A in tumors
Authors: Zhang Cai , Niu Jiafeng , Zhang Jianhua , Wang Yiping , Zhou Zhixia , Zhang Jian , Tian Zhigang
Published: April 2008

Natural killer cells are an important component of innate resistance to viruses, bacteria, certain parasites, and tumors. The activating receptor natural killer group 2D (NKG2D) plays a critical role in the elimination of tumor cells by cytotoxic effector cells. It has been shown that the strength of an antitumor immune response might be critically dependent on NKG2D ligard surface levels. Thus, it is essential to regulate the expression of NKG2D ligands in order to ensure effective tumor immunosurveillance and the elimination of pathogen‐infected cells. In the present study, we found that interferon (IFN)‐α and IFNγ exert opposing effects on major histocompatibility complex class I‐related chain A (MICA) expression in human tumor cells. IFNα promotes expression of the NKG2D ligand MICA in tumor cells and therefore enhances their sensitivity to natural killer lysis. In contrast, IFNγ exerts the opposite effect. IFNα promotes MICA expression at the level of transcription by augmenting MICA promoter activity. IFNγ modulates MICA expression not only at the transcriptional level, but also at the post‐translational level by promoting proteolytic cleavage by matrix metalloproteinases. Further study is needed to clarify the precise regulatory mechanisms. The pathways involved in NKG2D ligand induction might represent a promising target for improving immune responses to cancer or infections. (Cancer Sci 2008; 99: 1279–1286)
Sonic hedgehog derived from human pancreatic cancer cells augments angiogenic function of endothelial progenitor cells
Authors: Yamazaki Madoka , Nakamura Kazumasa , Mizukami Yusuke , Ii Masaaki , Sasajima Junpei , Sugiyama Yoshiaki , Nishikawa Tomoya , Nakano Yasuhiro , Yanagawa Nobuyuki , Sato Kazuya , Maemoto Atsuo , Tanno Satoshi , Okumura Toshikatsu , Karasaki Hidenori , Kono Toru , Fujiya Mikihiro , Ashida Toshifumi , Chung Daniel C. , Kohgo Yutaka
Published: April 2008

Hedgehog signaling is important in the pathogenesis of pancreatic cancer. Several recent observations suggest the involvement of sonic hedgehog (SHH) in postnatal neovascularization. We identified a novel role for SHH in tumor‐associated angiogenesis in pancreatic cancer. Immunohistochemical analysis revealed that patched homolog 1 (PTCH1), both a receptor for and transcriptional target of hedgehog signaling, was expressed in a small fraction of endothelial cells within pancreatic cancer, but not in normal pancreatic tissue. When endothelial progenitor cells (EPC) isolated from human peripheral blood were cultured with supernatant from SHH‐transfected 293 cells or pancreatic cancer cells, mRNA levels of vascular endothelial growth factor (VEGF), stromal cell‐derived factor‐1 and angiopoietin‐1 were significantly increased, whereas no such induction was observed in human umbilical vein endothelial cell (HUVEC) and human dermal microvascular endothelial cell (HMVEC). HUVEC tube formation was stimulated when cocultured with EPC, and preconditioning EPC with supernatant from KP‐1 N pancreatic cancer cells highly expressing SHH significantly enhanced the effect. The effect was partially attenuated by specific inhibition of SHH with cyclopamine or a neutralizing antibody. These findings suggest that tumor‐derived SHH can induce angiogenesis, and this is mediated by its effects on EPC specifically. Targeting SHH would be a novel therapeutic approach that can inhibit not only proliferation of cancer cells but also EPC‐mediated angiogenesis. (Cancer Sci 2008; 99: 1131–1138)
Midkine and its clinical significance in endometrial carcinoma
Authors: Tanabe Kojiro , Matsumoto Mitsuyo , Ikematsu Shinya , Nagase Satoru , Hatakeyama Atsushi , Takano Tadao , Niikura Hitoshi , Ito Kiyoshi , Kadomatsu Kenji , Hayashi Shin‐ichi , Yaegashi Nobuo
Published: April 2008

Midkine (MK) is a secreted heparin‐binding growth factor. Several types of human cancer have increased MK expression with elevated serum levels. The purpose of this study was to determine whether MK was expressed in endometrial carcinoma and to evaluate the clinicopathological significance of serum MK in patients with endometrial carcinoma. Immunohistochemical expression of MK was evaluated in 85 endometrial carcinoma samples and 33 controls. MK expression was significantly higher in the carcinomas than in normal endometrium (P < 0.001). Interestingly, MK expression was highest at the margins of invasion and low in the superficial areas of the tumor samples. Using ELISA, we compared serum MK concentration in 120 endometrial carcinoma patients with the concentration in 46 patients with benign gynecologic tumors. Serum MK value in patients with cancer was significantly higher than that in the patients with benign diseases (P = 0.01). Patients with positive lymph node metastasis or recurrence, or cancer death, had a higher serum MK level (P = 0.008,P = 0.009, respectively). In conclusion, MK immunoreactivity in endometrial carcinoma is significantly higher than in normal endometrium. Additionally, preoperative serum MK levels are significantly correlated with prognosis and the presence of lymph node metastasis. Thus, MK may be a useful serum biomarker for identifying high risk patients of endometrial carcinoma. (Cancer Sci2008; 99: 1125–1130)
Reduced risk of endometrial cancer from alcohol drinking in Japanese
Authors: Hosono Satoyo , Matsuo Keitaro , Kajiyama Hiroaki , Hirose Kaoru , Suzuki Takeshi , Hiraki Akio , Kawase Takakazu , Kidokoro Kumiko , Nakanishi Toru , Hamajima Nobuyuki , Kikkawa Fumitaka , Tajima Kazuo , Tanaka Hideo
Published: April 2008

The role of alcohol consumption in the etiology of endometrial cancer has not been clarified. To examine the association between alcohol consumption and endometrial cancer risk, we conducted a case‐control study with 148 histologically diagnosed incident endometrial cancer cases and 1468 matched non‐cancer controls. Median consumption of alcohol was only 19.3 g/week among cases who drank and 28.2 g/week among controls who drank. These values are lower than in Western countries. Relative risk was analyzed in subjects classified into four groups according to weekly alcohol consumption (non‐drinkers, 1–24 g/week, 25–175 g/week, and >175 g/week). Confounder‐adjusted odds ratios for those consuming alcohol at <25 g/week, 25–175 g/week, and >175 g/week compared to non‐drinkers were 0.79 (95% confidence interval (CI), 0.49–1.28), 0.42 (95% CI, 0.23–0.79), and 0.47 (95% CI, 0.14–1.58), respectively. Further analysis was conducted concerning self‐reported physical reaction to alcohol. Among women without flushing after drinking, a significant inverse association between risk and alcohol intake was seen (trend P = 0.001). In contrast, no protective effect of alcohol was seen among women who experience flushing after drinking. These results suggest the presence of an inverse association between alcohol drinking and endometrial cancer risk among Japanese women, and that this association is evident among those without flushing. Further investigation of these findings is warranted. (Cancer Sci 2008; 99: 1195–1201)
Exon 19 of EGFR mutation in relation to the CA‐repeat polymorphism in intron 1
Authors: Sueoka‐Aragane Naoko , Imai Kazue , Komiya Kazutoshi , Sato Akemi , Tomimasu Rika , Hisatomi Takashi , Sakuragi Toru , Mitsuoka Masahiro , Hayashi Shinichiro , Nakachi Kei , Sueoka Eisaburo
Published: April 2008

Epidermal growth factor receptor (EGFR) mutations in lung cancer enhance tyrosine kinase activity and increase sensitivity to the EGFR tyrosine kinase inhibitor, gefitinib. Mutation analysis of the EGFR gene is therefore indispensable for predicting gefitinib response. We investigated a CA‐repeat polymorphism in the EGFR gene related to EGFR mutations. Because an increasing number of CA‐repeats at intron 1 of the EGFR gene has been reported to reduce transcription activity, we examined the relationship between EGFR mutations and this CA‐repeat polymorphism. EGFR mutations at exon 19 were closely associated with shorter CA‐repeat length in the shorter allele, but this was not the case for EGFR mutations at exons 18 or 21. Increased intrinsic EGFR mRNA expression in non‐cancerous lung tissues from lung adenocarcinoma patients was also significantly associated with shorter CA‐repeat length. A higher frequency of EGFR mutations at exon 19 was associated with shorter CA‐repeat length only in patients with high levels of EGFR mRNA expression. To determine the phenotypes of cells possessing shorter CA‐repeats, an in vitro study using human bronchial epithelial cells with different CA‐repeat lengths was performed; more rapid cell growth and activated EGF/EGFR signaling were found more often in the cells having both shorter CA‐repeats and increased EGFR mRNA expression. These results suggest that CA‐repeat length in the EGFR gene may be a genetic factor related to cancer in the case of EGFR mutations at exon 19. The mechanism likely involves enhanced intrinsic expression of EGFR mRNA and activated EGF/EGFR signaling that accompany shorter CA‐repeats. (Cancer Sci 2008; 99: 1180–1187)
Risk stratification and venous thromboprophylaxis in hospitalized medical and cancer patients
Authors: Prandoni Paolo , Samama Michel M.
Published: April 2008

Acute venous thromboembolism (VTE) is a serious and potentially fatal disorder, which often complicates the course of hospitalized medical patients. This is particularly true for carriers of malignant diseases. While the introduction of thromboprophylactic measures has probably affected the occurrence of postoperative VTE, there is an increasing awareness of the importance of medical conditions in determining thromboembolic events. Simple and clinically relevant risk assessment models are available to facilitate VTE risk assessment in hospitalized medical patients. Their validation in prospective studies is in progress. Randomized controlled clinical trials have consistently documented the efficacy of heparins and fondaparinux for prevention of VTE in hospitalized medical patients with a minimal haemorrhagic risk. Recognition of the incidence and clinical importance of thrombosis will probably encourage more widespread use of antithrombotic prophylaxis in medical patients and especially in some particular types of malignancies.
Recent advances in the pathogenesis and management of juvenile myelomonocytic leukaemia
Authors: Koike Kenichi , Matsuda Kazuyuki
Published: April 2008

Juvenile myelomonocytic leukaemia (JMML) is a fatal, mixed myeloproliferative and myelodysplastic disorder of early childhood. A number of significant advances have been achieved in recent years. The present review will focus on the pathogenesis and management of JMML. Specific defects in the RAS signalling pathway, which make JMML cells hypersensitive to granulocyte‐macrophage colony‐stimulating factor, are observed in at least two‐thirds of patients with JMML: inactivation of NF1 or mutations in NRAS, KRAS2 or PTPN11. Allogeneic haematopoietic stem cell transplantation is currently the only treatment able to cure JMML, although the high postrelapse rate is of great concern. We also review molecularly targeted therapeutics that interfere with the disrupted activation of the RAS signal transduction pathway.
β‐catenin signalling in mesenchymal islet‐derived precursor cells
Authors: Ikonomou L. , Geras‐Raaka E. , Raaka B. M. , Gershengorn M. C.
Published: April 2008

Abstract.  Objectives: Previously, we characterized human islet‐derived precursor cells (hIPCs) as mesenchymal stem cells that migrate out from islets in vitro and can differentiate into functional islet‐like structures following proliferative expansion. Here, we investigate the role of β‐catenin signalling in derivation and proliferation of hIPCs. Materials and methods: Localization of β‐catenin was performed using confocal microscopy. Expression levels of β‐catenin target genes were measured by quantitative real‐time polymerase chain reaction. Loss‐of‐function studies were performed using specific short interfering RNAs. Results: Immunostaining of islet outgrowths revealed translocation of β‐catenin from plasma membranes in intact islets to the nucleus in cells migrating out. There were no nuclear β‐catenin‐positive cells in intact islets whereas between 35% and 70% of cells in established hIPC cultures exhibited nuclear β‐catenin. Transcripts for β‐catenin target genes were increased in hIPCs compared to those in islets. β‐Catenin translocated to the cell membrane when hIPCs formed epithelial cell clusters. In proliferating hIPCs, there was a strong correlation between markers of proliferation and nuclear β‐catenin. Treatment of hIPCs with the glycogen synthase kinase‐3β inhibitor (2′Z,3′E)‐6‐Bromoindirubin‐3′‐oxime increased intracellular β‐catenin but reduced nuclear β‐catenin, and was associated with reduced cell proliferation. Finally, knockdown of β‐catenin decreased β‐catenin target gene expression and hIPC proliferation. Conclusions: These results support a functional role for β‐catenin during proliferation of hIPCs and suggest that activated β‐catenin signalling may also be important during hIPC derivation from islets.
Human adipose tissue stromal vascular fraction cells differentiate depending on distinct types of media
Authors: Balwierz A. , Czech U. , Polus A. , Filipkowski R. K. , Mioduszewska B. , Proszynski T. , Kolodziejczyk P. , Skrzeczynska‐Moncznik J. , Dudek W. , Kaczmarek L. , Kulig J. , Pryjma J. , Dembinska‐Kiec A.
Published: April 2008

Abstract.  Objectives: Angiogenesis, the process of formation of blood vessels, is essential for many physiological as well as pathological processes. It has been shown that human adipose tissue contains a population of non‐characterized cells, called stromal‐vascular fraction (SVF) cells, which are able to differentiate into several lineages. The aim of this study was to determine conditions for promoting differentiation of human adipose tissue progenitors towards endothelial cells, as well as to show that SVF cells cooperate with differentiated endothelium in capillary network formation. Materials and methods: Stromal vascular fraction cells were isolated according to modified Hauner's method and after adaptation they were cultured in pro‐angiogenic or pro‐adipogenic medium. Cells were characterized by presence of surface antigens by flow cytometry, and by expression of genes characteristic for endothelial cells or for adipocytes, quantitative real‐time polymerase chain reaction. A number of tests were performed to verify their differentiation. Results: Differentiation of human SVF cells towards endothelium was stimulated by the presence of serum and absence of adipogenic factors, documented by the pattern of gene expression as well as different functional in vitro assays. SVF cells were found to work together with human umbilical vein endothelial cells to form capillary networks. Conclusions: Here, we show that differentiation of SVF cells to endothelial cells or adipocyte‐like cells depended on the medium used. Our work provides a clear model for analysing the differentiation capacity of SVF cells.
Profilin sensitization detected in the office by skin prick test: a study of prevalence and clinical relevance of profilin as a plant food allergen
Authors: Asero R. , Monsalve R. , Barber D.
Published: April 2008

Background
Profilin, a pan‐allergen present in all eukaryotic cells, is one of the main causes of cross‐sensitization between pollen and plant‐derived foods, but its clinical relevance as a food allergen is still debated.

Objective
To investigate the prevalence of profilin sensitization in a pollen‐allergic population and its clinical relevance as a food allergen.

Methods
Two hundred consecutive patients with pollen allergy underwent skin prick tests (SPT) with purified natural date palm profilin (Pho d 2; 50 μg/mL; Alk Abello, Madrid, Spain). Those reporting adverse reactions to foods (confirmed by SPT with either commercial food extracts or fresh foods) underwent SPT with an apple extract containing uniquely Mal d 1 (2 μg/mL; ALK‐Abello), and with a commercial peach extract containing uniquely lipid transfer protein (LTP 30 μg/mL; ALK‐Abello).

Results
Sixty patients (30%) showed skin reactivity to date palm profilin, Pho d 2. All were sensitized to grass pollen, and most of them reacted to birch, mugwort, ragweed and plantain pollen as well. SPT with pellitory and cypress scored negative in a high proportion of profilin reactors [26/60 (43%) and 33/60 (55%), respectively]. More than one half (34/60 [57%]) of profilin reactors had food allergy; 21 of these were monosensitized to profilin, 11 were sensitized to both profilin and Bet v 1 homologous protein, one to both profilin and LTP, and one to all the three allergens. The large majority of profilin‐allergic patients reported oral allergy syndrome as the only food‐induced symptom and were able to tolerate the offending foods if they were cooked or otherwise processed. Twenty‐eight of 34 reported reactivity to two or more plant‐derived foods. Rosaceae, tree nuts, melon and watermelon, tomato, pineapple, citrus fruits and banana were the more frequently offending foods.

Conclusion
Profilin should be considered a clinically relevant food allergen. Allergy to melon, watermelon, tomato, banana, pineapple and orange may be considered as a marker of profilin hypersensitivity. This study underlines the clinical importance of being able to diagnose hypersensitivity to single food allergenic proteins by SPT, particularly when the relevant food allergen sources contain several allergens that show different chemical/physical features and, hence, completely different risk profiles.
The development of atopic dermatitis is independent of Immunoglobulin E up‐regulation in the K14‐IL‐4 SKH1 transgenic mouse model
Authors: Chen L. , Overbergh L. , Mathieu C. , Chan L. S.
Published: April 2008

Background
We have successfully generated an IgE‐associated (extrinsic/allergic) mouse model of atopic dermatitis in K14‐IL‐4‐Tg/CByB6 mice. The newly described subset of non‐IgE‐associated (intrinsic/non‐allergic) atopic dermatitis in human patients raises the question on the role of IgE in the pathogenesis.

Objective
The aim of this study was to develop a non‐IgE‐associated atopic dermatitis model in K14‐IL‐4‐Tg/SKH1 mice.

Methods
K14‐IL‐4‐Tg/CByB6 mice were crossed with SKH1 mice to produce K14‐IL‐4‐Tg/SKH1 mice. Phenotypes of clinical and histological, cytokine expression in the skin lesions, and total serum IgE in K14‐IL‐4‐Tg/CByB6 and K14‐IL‐4‐Tg/SKH1 mice were compared. The CD40 and CD40L on T and B cells were also studied to differentiate their roles in IgE production.

Results
K14‐IL‐4‐Tg/SKH1mice had a normal total serum IgE level and manifested a chronic inflammatory skin phenotype identical to that of K14‐IL‐4‐Tg/CByB6 IgE‐mediated mice in clinical morphology, histology, infiltration of mononuclear cells/eosinophils/mast cells, mast cell degranulation, and up‐regulation of chronic lesional cytokine mRNA expression of IL‐1β, IL‐3, IL‐4, IL‐6, IL‐10, IL‐12, IL‐13, IFN‐γ, TNF‐α, and TNF‐β. We also found that the inability of CD4+ T cells of the K14‐IL‐4‐Tg/SKH1mice to up‐regulate CD40L expression upon stimulation might account for their inability to up‐regulate the IgE level. B cell abnormality was ruled out as CD19+ B cells of K14‐IL‐4‐Tg/SKH1 mice synthesized the same amount of IgE in vitro compared with K14‐IL‐4‐Tg/CByB6 mice in the presence of IL‐4 and soluble CD40L. Our studies further suggested that the defect of early growth response‐1 in T cells might be responsible for the impaired CD40L up‐regulation in K14‐IL‐4‐Tg/SKH1 mice.

Conclusion
K14‐IL‐4‐Tg/SKH1 mice developed skin inflammation that resembled human intrinsic atopic dermatitis. Therefore, this model may be suitable to study the pathogenesis of intrinsic atopic dermatitis.
Detection of somatic β‐catenin mutations in primary pigmented nodular adrenocortical disease (PPNAD)
Authors: Tadjine Mimi , Lampron Antoine , Ouadi Lydia , Horvath Anelia , Stratakis Constantine A. , Bourdeau Isabelle
Published: April 2008

Background  Primary pigmented nodular adrenocortical disease (PPNAD) leads to Cushing syndrome (CS) and is often associated with Carney complex (CNC). Genetic alterations of the type 1‐α regulatory subunit of cAMP‐dependent protein kinase A (PRKAR1A) and phosphodiesterase 11A4 (PDE11A) genes have been found in PPNAD. Recent studies have demonstrated that β‐catenin mutations are frequent in adrenocortical adenomas and carcinomas and that the Wnt‐signalling pathway is involved in PPNAD tumorigenesis. We hypothesized that adrenocortical adenomas that form in the context of PPNAD may harbour β‐catenin mutations.

Methods  We studied 18 patients with CS secondary to PPNAD who were screened for germline PRKAR1A and PDE11A mutations. Tumor DNA was extracted from pigmented adrenocortical adenoma and nodular adrenal hyperplasia. Mutation analysis of exons 3 and 5 of β‐catenin was performed using polymerase chain reaction and direct sequencing. Sections from formalin‐fixed, paraffin‐embedded tumour samples were studied by immunohistochemistry with an antibody against β‐catenin.

Results  Nine patients were carrying germline PRKAR1A mutations and one patient had a PDE11A mutation. We found somatic β‐catenin mutations in 2 of 18 patients (11%). In both cases, the mutations occurred in relatively large adenomas that had formed in the background of PPNAD. Tumor DNA analysis revealed a heterozygous ACC‐to‐GCC missense mutation in codon 41 (T41A) and a TCT‐to‐CCT missense mutation in codon 45 (S45P) of exon 3 of the β‐catenin gene that was confirmed at the cDNA level. There were no alterations in the DNA of PPNAD‐adjacent tissues and lymphocytes from the patients, indicating somatic events. Immunohistochemistry showed nuclear accumulation of β‐catenin in more than 90% of cells in adenomatous tissue whereas no nuclear immunoreactivity was detected in adjacent PPNAD nodular cells. Nuclear translocation of β‐catenin protein in the PPNAD adenoma suggests activation of the Wnt–β‐catenin pathway in PPNAD.

Conclusions  We report, for the first time, β‐catenin mutations in adenomas associated with PPNAD, further implicating Wnt–β‐catenin signalling in tumorigenesis linked to bilateral adrenal hyperplasias.
A comparison of the relative contributions of temporal and spatial variation in the density of drifting invertebrates in a Dorset (U.K.) chalk stream
Authors: NEALE MARTIN W. , DUNBAR MICHAEL J. , JONES J. IWAN , IBBOTSON ANTON T.
Published: April 2008

1. Invertebrate drift is commonly investigated in streams, with the majority of studies focussed on temporal (typically diel) variation. In comparison, few studies have investigated spatial variation in drift and there is little consensus among them. We tested the hypothesis that spatial variation in invertebrate drift is as important as temporal variation.

2. The density of drifting invertebrates in a chalk stream was sampled using an array of nets arranged to determine vertical, lateral and longitudinal variation. Samples were collected at dawn, during the day, at dusk and by night, on four separate monthly occasions. Insecta and Crustacea were analysed separately to identify the effect of differing life history strategies. The density of drifting debris was also recorded, to act as a null model.

3. Time of day and vertical position together explained the majority of the variance in invertebrate drift (79% for Insecta and 97% for Crustacea), with drift densities higher at dusk and night, and nearer the stream bed. Independently, time of day (38%, Insecta; 52%, Crustacea) and vertical position (41%, Insecta; 45%, Crustacea) explained a similar amount of the observed variance. Month explained some of the variance in insect drift (9%) but none for Crustacea.

4. Variation in the density of drifting debris showed little in common with invertebrate drift. There was little variation associated with time of day and only 27% of the observed variation in debris could be explained by the factors investigated here, with month explaining the largest proportion (20%). We suggest the difference in drifting debris and invertebrates provides further evidence for a strong behavioural component in invertebrate drift.

5. Spatial variation in invertebrate drift can be of the same order of magnitude as the much‐described diel temporal variation. The extent of this spatial variation poses problems when attempting to quantify invertebrate drift and we recommend that spatial replication should be incorporated into drift studies.
Cysteine protease cathepsin X modulates immune response via activation of β2 integrins
Authors: Obermajer Nataša , Repnik Urška , Jevnikar Zala , Turk Boris , Kreft Marko , Kos Janko
Published: April 2008

Cathepsin X is a lysosomal, cysteine dependent carboxypeptidase. Its expression is restricted to cells of the immune system, suggesting a function related to the processes of inflammatory and immune responses. It has been shown to stimulate macrophage antigen‐1 (Mac‐1) receptor‐dependent adhesion and phagocytosis via interaction with integrin β2 subunit. Here its potential role in regulating lymphocyte proliferation via Mac‐1 and the other β2 integrin receptor, lymphocyte function‐associated antigen‐1 (LFA‐1) has been investigated. Cathepsin X has been shown to suppress proliferation of human peripheral blood mononuclear cells, by activation of Mac‐1, known as a suppressive factor for lymphocyte proliferation. On the other hand, co‐localization of cathepsin X and LFA‐1 supports the role of cathepsin X in regulating LFA‐1 activity, which enhances lymphocyte proliferation. As shown by fluorescence resonance energy transfer, using U‐937 and Jurkat cells transfected with αL‐mCFP and β2‐mYFP, recombinant cathepsin X directly activates LFA‐1. The activation was confirmed by increased binding of monoclonal antibody 24, recognizing active LFA‐1. We demonstrate that cathepsin X is involved in the regulation of two β2 integrin receptors, LFA‐1 and Mac‐1, which exhibit opposing roles in lymphocyte activation.
H2‐Dd‐mediated upregulation of interleukin‐4 production by natural killer T‐cell and dendritic cell interaction
Authors: Mizuuchi Kazuomi , Yanagawa Yoshiki , Iwabuchi Kazuya , Namba Kenichi , Kitaichi Nobuyoshi , Ohno Shigeaki , Onoé Kazunori
Published: April 2008

Natural killer T (NKT) cells are capable of subserving apparently opposite functions, the interferon‐γ (IFN‐γ)‐mediated enhancement of host defence and interleukin‐4 (IL‐4) ‐mediated immune regulation. Although dendritic cells (DCs) potently activate NKT cells, DC regulation of the IL‐4–IFN‐γ balance via NKT‐cell activation is not well characterized. In the present study, we examined the effect of DC treatment with CpG oligodeoxynucleotide (ODN), a Toll‐like receptor 9 ligand, on the induction of NKT‐cell cytokine production. CpG‐ODN‐conditioned and α‐galactosylceramide (α‐GalCer)‐loaded myeloid DCs (CpG‐DCs) from BALB/c mice showed enhanced ability to induce NKT‐cell production of IL‐4, but not IFN‐γ, compared to α‐GalCer‐loaded control DCs (not treated with CpG‐ODN). The CpG‐DCs expressed significantly higher levels of H2‐Dd than control DCs, and blocking of the H2‐Dd and Ly49 receptor interaction during antigen presentation completely abolished the enhanced ability of the CpG‐DCs to induce NKT‐cell production of IL‐4. These findings demonstrate that DC recognition of the CpG motif leads to induction of enhanced IL‐4 production by NKT cells via interaction of the augmented H2‐Dd with Ly49 receptors on NKT cells.