bluuebunny/crossref_metadata_2025 huggingface dataset:
Microscale inverse acoustic band gap structure in aluminum nitride
Authors: Kuo Nai-Kuei , Zuo Chengjie , Piazza Gianluca
Published: September 2009

This work presents the design and demonstration of a microscale inverse acoustic band gap (IABG) structure in aluminum nitride (AlN) with a frequency stop band for bulk acoustic waves in the very high frequency range. Conversely to conventional microscale acoustic band gaps, the IABG is formed by a two-dimensional periodic array of unit cells consisting of a high acoustic velocity material cylinder surrounded by a low acoustic velocity medium. The periodic arrangement of the IABG array induces scattering of incident acoustic waves and generates a stop band, whose center frequency is primarily determined by the lattice constant of the unit cell and whose bandwidth depends on the cylinder radius, the film thickness, and the size of the tethers that support the cylinder. A wide band gap (>13% of the center frequency) is formed by the IABG even when thin AlN films are used. The experimental response of an IABG structure having a unit cell of 8.6 μm and an AlN film thickness of 2 μm confirms the existence of a frequency band gap between 185 MHz and 240 MHz.
Bubble velocity measurement using magnetic fluid and electromagnetic induction
Authors: Kuwahara Takuya , De Vuyst Florian , Yamaguchi Hiroshi
Published: September 2009

Bubble velocity is one of the important parameters in both fundamental studies and applications utilizing gas-liquid two-phase flow. However there are few models to estimate a bubble velocity. Even in existing models, the applicable range of a model is limited by flow condition and/or type of fluid. Another way to find a bubble velocity is measurement. A preferable measurement is a low cost and mechanically noncontact method with the fluid of interest to maintain the original bubble velocity. The method that satisfies these requirements is a measurement using optical visualization up to date. An optical visualization method is also seldom applied to the measurement in the case of complex two-phase flow. In the present paper, a measurement using magnetic fluid and electromagnetic induction is proposed. A setup, theory, and algorithm for the measurement are established. To evaluate the method, the measurements are carried out in real gas-liquid flows. One is an uprising single bubble (Taylor bubble) in a static liquid to obtain a fundamental insight. Another is an ordinary gas-liquid two-phase flow to confirm the applicability in complex flows. The measured bubble velocities are compared to those from the optical visualization and existing models. As a result, the present method provides appropriate velocities. The result concludes that the proposed method is utilizable as a bubble velocity measurement.
Density functional study of flexible chain molecules at curved surfaces
Authors: Hlushak S. P. , Rżysko W. , Sokołowski S.
Published: September 2009

Density profiles of flexible hard-sphere chain molecules in hard cylindrical pores and around hard cylindrical rods of various diameters were obtained by means of density functional theory of Yu and Wu [Y.-X. Yu and J. Wu, J. Chem. Phys. 117, 2368 (2002)] and grandcanonical Monte Carlo simulation. The density profiles show stronger depletion of long chain molecules from narrow cylindrical pores at low densities, when compared to slit pores of the same width. Additionally, positive surface curvature of cylindrical pores increases the magnitude of wall depletion of chain molecules at low and intermediate densities. For negative surfaces curvature around the cylindrical rod, the wall depletion of chains is weaker than for a flat surface.
A fast path integral method for polarizable force fields
Authors: Fanourgakis George S. , Markland Thomas E. , Manolopoulos David E.
Published: September 2009

A quantum simulation of an imaginary time path integral typically requires around n times more computational effort than the corresponding classical simulation, where n is the number of ring polymer beads (or imaginary time slices) used in the calculation. It is however possible to improve on this estimate by decomposing the potential into a sum of slowly and rapidly varying contributions. If the slowly varying contribution changes only slightly over the length scale of the ring polymer, it can be evaluated on a contracted ring polymer with fewer than the full n beads (or equivalently on a lower order Fourier decomposition of the imaginary time path). Here we develop and test this idea for systems with polarizable force fields. The development consists of iterating the induction on the contracted ring polymer and applying an appropriate transformation to obtain the forces on the original n beads. In combination with a splitting of the Coulomb potential into its short- and long-range parts, this results in a method with little more than classical computational effort in the limit of large system size. The method is illustrated with simulations of liquid water at 300 K and hexagonal ice at 100 K using a recently developed flexible and polarizable Thole-type potential energy model.
A method of determining narrow energy spread electron beams from a laser plasma wakefield accelerator using undulator radiation
Authors: Gallacher J. G. , Anania M. P. , Brunetti E. , Budde F. , Debus A. , Ersfeld B. , Haupt K. , Islam M. R. , Jäckel O. , Pfotenhauer S. , Reitsma A. J. W. , Rohwer E. , Schlenvoigt H.-P. , Schwoerer H. , Shanks R. P. , Wiggins S. M. , Jaroszynski D. A.
Published: September 2009

In this paper a new method of determining the energy spread of a relativistic electron beam from a laser-driven plasma wakefield accelerator by measuring radiation from an undulator is presented. This could be used to determine the beam characteristics of multi-GeV accelerators where conventional spectrometers are very large and cumbersome. Simultaneous measurement of the energy spectra of electrons from the wakefield accelerator in the 55–70 MeV range and the radiation spectra in the wavelength range of 700–900 nm of synchrotron radiation emitted from a 50 period undulator confirm a narrow energy spread for electrons accelerated over the dephasing distance where beam loading leads to energy compression. Measured energy spreads of less than 1% indicates the potential of using a wakefield accelerator as a driver of future compact and brilliant ultrashort pulse synchrotron sources and free-electron lasers that require high peak brightness beams.
Arbitrary multisite two-photon excitation in four dimensions
Authors: Daria Vincent Ricardo , Stricker Christian , Bowman Richard , Redman Stephen , Bachor Hans-A.
Published: September 2009

We demonstrate dynamic and arbitrary multisite two-photon excitation in three dimensions using the holographic projection method. Rapid response (fourth dimension) is achieved through high-speed noniterative calculation of the hologram using a video graphics accelerator board. We verify that the projected asymmetric spot configurations have sufficient spatiotemporal photon density for localized two-photon excitation. This system is a significant advance and can be applied to time-resolved photolysis of caged compounds in biological cells and complex neuronal networks, nonlinear microfabrication and volume holographic optical storage.
Imprint in ferroelectric materials due to space charges: A theoretical analysis
Authors: Okatan M. B. , Alpay S. P.
Published: September 2009

Imprint is a degradation mechanism in ferroelectrics that results in the displacement of the polarization hysteresis loop along the electric field axis. We develop a model using a nonlinear thermodynamic analysis coupled with electrostatics to show that such internal voltage offsets can originate from asymmetrically distributed trapped space charges. The electrostatic interactions are established through a built-in polarization due to the space charges and the spontaneous polarization. Numerical results for Ba0.8Sr0.2TiO3 show that the maximum electric field offset does not necessarily occur due to charges trapped near the electrodes.
Electromagnetic waves in dusty magnetoplasmas using two-potential theory
Authors: Zubia K. , Jamil M. , Salimullah M.
Published: September 2009

The low-frequency long wavelength electromagnetic waves, viz., shear Alfvén waves in a cold dusty plasma, have been examined employing two-potential theory and plasma fluid model. The presence of the unmagnetized dust particles and magnetized plasma components gives rise to a new ion-dust lower hybrid cutoff frequency for the electromagnetic shear Alfvén wave propagation. The importance and relevance of the present work to the space dusty plasma environments are also pointed out.
Comparative systems biology across an evolutionary gradient within the
Shewanella
genus
Authors: Konstantinidis Konstantinos T. , Serres Margrethe H. , Romine Margaret F. , Rodrigues Jorge L. M. , Auchtung Jennifer , McCue Lee-Ann , Lipton Mary S. , Obraztsova Anna , Giometti Carol S. , Nealson Kenneth H. , Fredrickson James K. , Tiedje James M.
Published: September 2009

To what extent genotypic differences translate to phenotypic variation remains a poorly understood issue of paramount importance for several cornerstone concepts of microbiology including the species definition. Here, we take advantage of the completed genomic sequences, expressed proteomic profiles, and physiological studies of 10 closely related
Shewanella
strains and species to provide quantitative insights into this issue. Our analyses revealed that, despite extensive horizontal gene transfer within these genomes, the genotypic and phenotypic similarities among the organisms were generally predictable from their evolutionary relatedness. The power of the predictions depended on the degree of ecological specialization of the organisms evaluated. Using the gradient of evolutionary relatedness formed by these genomes, we were able to partly isolate the effect of ecology from that of evolutionary divergence and to rank the different cellular functions in terms of their rates of evolution. Our ranking also revealed that whole-cell protein expression differences among these organisms, when the organisms were grown under identical conditions, were relatively larger than differences at the genome level, suggesting that similarity in gene regulation and expression should constitute another important parameter for (new) species description. Collectively, our results provide important new information toward beginning a systems-level understanding of bacterial species and genera.
Secretin as a neurohypophysial factor regulating body water homeostasis
Authors: Chu Jessica Y. S. , Lee Leo T. O. , Lai C. H. , Vaudry H. , Chan Y. S. , Yung W. H. , Chow Billy K. C.
Published: September 2009

Hypothalamic magnocellular neurons express either one of the neurohypophysial hormones, vasopressin or oxytocin, along with different neuropeptides or neuromodulators. Axonal terminals of these neurons are generally accepted to release solely the two hormones but not others into the circulation. Here, we show that secretin, originally isolated from upper intestinal mucosal extract, is present throughout the hypothalamo–neurohypophysial axis and that it is released from the posterior pituitary under plasma hyperosmolality conditions. In the hypothalamus, it stimulates vasopressin expression and release. Considering these findings together with our previous findings that show a direct effect of secretin on renal water reabsorption, we propose here that secretin works at multiple levels in the hypothalamus, pituitary, and kidney to regulate water homeostasis. Findings presented here challenge previous understanding regarding the neurohypophysis and could provide new concepts in treating disorders related to osmoregulation.
Acp36DE is required for uterine conformational changes in mated Drosophila females
Authors: Avila Frank W. , Wolfner Mariana F.
Published: September 2009

In a multitude of animals with internal fertilization, including insects and mammals, sperm are stored within a female's reproductive tract after mating. Defects in the process of sperm storage drastically reduce reproductive success. In
Drosophila
males, “Acp” seminal proteins alter female postmating physiology and behavior, and are necessary for several aspects of sperm storage. For example, Acps cause a series of conformational changes in the mated female's reproductive tract that occur during and immediately after mating. These conformational changes have been hypothesized to aid both in the movement of sperm within the female and in the subsequent storage of those sperm. We used RNAi to systematically knock down several Acps involved in sperm storage to determine whether they played a role in the mating-induced uterine conformational changes. Mates of males lacking the glycoprotein Acp36DE, which is needed for the accumulation of sperm in the storage organs, fail to complete the full sequence of the conformational changes. Our results show that uterine conformational changes are important for proper accumulation of sperm in storage and identify a seminal protein that mediates these changes. Four Acps included in this study, previously shown to affect sperm release from storage (CG9997, CG1656, CG1652, and CG17575), are not necessary for uterine conformational changes to occur. Rather, consistent with their role in later steps of sperm storage, we show here that their presence can affect the outcome of sperm competition situations.
RETRACTED: Identification of an RNA-dependent RNA polymerase in
Drosophila
involved in RNAi and transposon suppression
Authors: Lipardi Concetta , Paterson Bruce M.
Published: September 2009

Here, we show that recombinant
Drosophila
elp1 (D-elp1) produced in Sf9 cells or
Escherichia coli
, corresponding to the largest of the three subunits in the RNA polymerase II core elongator complex, has RNA-dependent RNA polymerase (RdRP) activity. D-elp1 is a noncanonical RdRP that can synthesize dsRNA from different ssRNA templates using either a primer-dependent or primer-independent initiation mechanism. Of the three core subunits, only D-elp1 depletion inhibits RNAi in S2 cells but does not affect micro RNA function. Furthermore, D-elp1 depletion results in increased steady state levels of representative transposon RNAs and a decrease in the corresponding transposon antisense transcripts and endo siRNAs. In contrast, although Dcr-2 depletion results in increased transposon RNA levels and a reduction in the corresponding endo siRNAs, there is no change in the transposon antisense RNA levels. In D-elp1 null third instar larvae transposon RNA levels are also increased and the corresponding transposon antisense RNAs are reduced. D-elp1 associates tightly with Dcr-2, similar to the Dicer-RdRP interaction observed in lower eukaryotes. These results identify an aspect of the RNAi pathway in
Drosophila
that suggest transposon derived endo siRNAs, critical for transposon suppression, are produced, in part, in a D-elp1 dependent step that converts transposon RNA into dsRNA that is subsequently processed by Dcr-2. The generality of this mechanism in genome defense and RNA silencing in higher eukaryotes is suggested.
The continuity of protein structure space is an intrinsic property of proteins
Authors: Skolnick Jeffrey , Arakaki Adrian K. , Lee Seung Yup , Brylinski Michal
Published: September 2009

The classical view of the space of protein structures is that it is populated by a discrete set of protein folds. For proteins up to 200 residues long, by using structural alignments and building upon ideas of the completeness and continuity of structure space, we show that nearly any structure is significantly related to any other using a transitive set of no more than 7 intermediate structurally related proteins. This result holds for all structures in the Protein Data Bank, even when structural relationships between evolutionary related proteins (as detected by threading or functional analyses) are excluded. A similar picture holds for an artificial library of compact, hydrogen-bonded, homopolypeptide structures. The 3 sets share the global connectivity features of random graphs, in which the local connectivity of each node (i.e., the number of neighboring structures per protein) is preserved. This high connectivity supports the continuous view of single-domain protein structure space. More importantly, these results do not depend on evolution, rather just on the physics of protein structures. The fact that evolutionary divergence need not be invoked to explain the continuous nature of protein structure space has implications for how the universe of protein structures might have originated, and how function should be transferred between proteins of similar structure.
Nod2 is required for the regulation of commensal microbiota in the intestine
Authors: Petnicki-Ocwieja Tanja , Hrncir Tomas , Liu Yuen-Joyce , Biswas Amlan , Hudcovic Tomas , Tlaskalova-Hogenova Helena , Kobayashi Koichi S.
Published: September 2009

Mutations in the
Nod2
gene are among the strongest genetic risk factors in the pathogenesis of ileal Crohn's disease, but the exact contributions of Nod2 to intestinal mucosal homeostasis are not understood. Here we show that Nod2 plays an essential role in controlling commensal bacterial flora in the intestine. Analysis of intestinal bacteria from the terminal ilea of
Nod2
-deficient mice showed that they harbor an increased load of commensal resident bacteria. Furthermore,
Nod2
-deficient mice had a diminished ability to prevent intestinal colonization of pathogenic bacteria. In vitro, intestinal crypts isolated from terminal ilea of
Nod2
-deficient mice were unable to kill bacteria effectively, suggesting an important role of Nod2 signaling in crypt function. Interestingly, the expression of
Nod2
is dependent on the presence of commensal bacteria, because mice re-derived into germ-free conditions expressed significantly less
Nod2
in their terminal ilea, and complementation of commensal bacteria into germ-free mice induced
Nod2
expression. Therefore, Nod2 and intestinal commensal bacterial flora maintain a balance by regulating each other through a feedback mechanism. Dysfunction of Nod2 results in a break-down of this homeostasis.
Antibody-mediated blockade of IL-15 reverses the autoimmune intestinal damage in transgenic mice that overexpress IL-15 in enterocytes
Authors: Yokoyama Seiji , Watanabe Nobumasa , Sato Noriko , Perera Pin-Yu , Filkoski Lyvouch , Tanaka Toshiyuki , Miyasaka Masayuki , Waldmann Thomas A. , Hiroi Takachika , Perera Liyanage P.
Published: September 2009

Celiac disease (CD) is an autoimmune inflammatory disease with a relatively high prevalence especially in the western hemisphere. A strong genetic component is involved in the pathogenesis of CD with virtually all individuals that develop the disease carrying HLA-DQ alleles that encode specific HLA-DQ2 or HLA-DQ8 heterodimers. Consumption of cereals rich in gluten triggers a chronic intestinal inflammation in genetically susceptible individuals leading to the development of CD. Emerging evidence has implicated a central role for IL-15 in the orchestration and perpetuation of inflammation and tissue destruction in CD. Therefore, IL-15 represents an attractive target for development of new therapies for CD. Transgenic mice that express human IL-15 specifically in enterocytes (T3b-hIL-15 Tg mice) develop villous atrophy and severe duodeno-jejunal inflammation with massive accumulation of NK-like CD8+lymphocytes in the affected mucosa. We used these mice to demonstrate that blockade of IL-15 signaling with an antibody (TM-β1) that binds to murine IL-2/IL-15Rbeta (CD122) leads to a reversal of the autoimmune intestinal damage. The present study, along with work of others, provides the rationale to explore IL-15 blockade as a test of the hypothesis that uncontrolled expression of IL-15 is critical in the pathogenesis and maintenance of refractory CD.
Diffusion-weighted magnetic resonance imaging of endometrial cancer: differentiation from benign endometrial lesions and preoperative assessment of myometrial invasion
Authors: Takeuchi M. , Matsuzaki K. , Nishitani H.
Published: September 2009

Background: Uterine endometrial cancer is the most common gynecologic malignancy, and benign endometrial hyperplasia or polyps should be differentiated from endometrial cancer. In evaluating endometrial cancer on magnetic resonance imaging (MRI), the assessment of the depth of myometrial invasion is important because it closely correlates with the patient's prognosis.

Purpose: To verify the feasibility of diffusion-weighted magnetic resonance imaging (DWI) to distinguish benign and malignant endometrial lesions, and to evaluate myometrial invasion of endometrial cancer.

Material and Methods: Sixty-seven endometrial lesions including 45 cancers and 22 benign lesions (hyperplasia and polyps) were evaluated by DWI with apparent diffusion coefficient (ADC) measurement. The staging accuracies of DWI and gadolinium-enhanced T1-weighted images in the assessment of myometrial invasion were evaluated in 33 patients with endometrial cancer.

Results: The ADC values (×10−3 mm2/s) in cancer and benign lesions were 0.84±0.19 and 1.58±0.36, respectively ( P<0.01). The staging accuracy (superficial or deep myometrial invasion) was 94% for DWI and 88% for gadolinium-enhanced T1-weighted images. Coexisting adenomyosis and infiltrative myometrial invasion caused staging errors on gadolinium-enhanced T1-weighted images, whereas DWI could demonstrate the tumor extent correctly.

Conclusion: DWI provides helpful information in evaluating benign and malignant endometrial lesions.
Your Job Is Your Credit: Creating a Market for Loans to Salaried Employees in New York City, 1885–1920
Authors: Easterly Michael
Published: September 2009

In the first decade of the twentieth century, a market in the personal debt of corporate and government employees was thriving in New York City and other major urban centers in the Northeastern andMidwestern United States. A set of shadowy entrepreneurs, colloquially known as “loan sharks,” offered short-term, high-rate advances that they called salary loans. Despite operating in violation of the law, primarily the prohibition against usury, the operations of these intermediaries had by 1912 reached an imposing scale. At least eighty-one such offices operated in Manhattan and Brooklyn alone, with millions of dollars in loans outstanding. Of these eighty-one offices, thirty-four belonged to interstate chains, the largest ofwhich stretched over sixtythree cities in the United States and Canada.
SIAH1 induced apoptosis by activation of the JNK pathway and inhibited invasion by inactivation of the ERK pathway in breast cancer cells
Authors: Wen Yuan‐Yuan , Yang Zhi‐Qiang , Song Min , Li Bai‐Lin , Zhu Ji‐Jiang , Wang En‐Hua
Published: September 2009

Seven in absentia homolog 1 (SIAH1), a homologue of Drosophila seven in absentia (Sina), has emerged as a tumor suppressor and plays an important role in regulating cell apoptosis. To investigate the role and possible mechanism of SIAH1 in breast cancer cells, we up‐regulated the expression of SIAH1 using pcDNA3‐myc‐SIAH1 and knocked down SIAH1 using SIAH1 siRNA. We found that the overexpression of SIAH1 induced cell apoptosis by up‐regulating the level of Bim through the activation of the JNK signaling pathway, and the suppression of SIAH1 expression increased cell invasion via the activation of the ERK signaling pathway in breast cancer cells. All these results indicate that the JNK and ERK signaling pathways may play an important role in the SIAH1‐dependent biological behavior of breast cancer, and it may be a good molecular therapeutic target to increase the expression level of SIAH1 through promoting cell apoptosis and inhibiting cell invasion in human breast cancer. (Cancer Sci 2009)
Immunoglobulin heavy chain variable region gene usage and mutational status of the leukemic B cells in Iranian patients with chronic lymphocytic leukemia
Authors: Hojjat‐Farsangi Mohammad , Jeddi‐Tehrani Mahmood , Razavi Seyed Mohsen , Sharifian Ramazan Ali , Mellstedt Hakan , Shokri Fazel , Rabbani Hodjatallah
Published: September 2009

The mutational status of the immunoglobulin variable region heavy chain genes (IGHV) is an important prognostic marker in chronic lymphocytic leukemia (CLL). The data accumulated in the literature has largely been derived from studies conducted on Caucasian Western populations. Little is known about Asian CLL patients. In this study the IGHV genes usage and somatic hypermutation status have been investigated in 87 Iranian CLL patients. Based on a cut‐off of 98% nucleotide sequence homology, 64.4% and 35.6% of the patients expressed mutated and unmutated IGHV genes, respectively, with most non‐progressive patients being in the mutated group (35/44 vs 19/40; P = 0.009). Progression‐free survival (PFS) and time to first treatment (TTFT) were significantly higher in our mutated and non‐progressive patients compared to unmutated and progressive subtypes, respectively. The most frequently used IGHV gene was IGHV3‐7 (12.6%) followed by IGHV3‐30 (11.4%), IGHV3‐48 (9.2%), IGHV4‐39 (6.9%), and IGHV1‐8 (6.9%) genes, which taken together comprised nearly half of the IGHV genes expressed in the Iranian CLL patients. Of the IGHV genes, IGHV3‐7 was significantly over‐represented in non‐progressive compared to progressive CLL patients (P = 0.036), whereas IGHV1‐69 and IGHV1‐2 were expressed at a higher frequency in unmutated compared to mutated CLL patients (P < 0.03). Comparison of IGHV gene usage in our patients with that of Western CLL patients revealed significant differences in expression of IGHV1‐69, IGHV3‐7, IGHV3‐21, and IGHV4‐34 genes. Analysis of the IGHV third complementary determining region (HCDR3) sequences revealed a high frequency use of certain HCDR3 motifs, such as YYYGMDV, in our samples. These findings imply contribution of antigen selection and regional (ethnic/geographic) parameters in the leukomogenesis of CLL. (Cancer Sci 2009; 100: 2346–2353)
Carcinogenic potential of alizarin and rubiadin, components of madder color, in a rat medium‐term multi‐organ bioassay
Authors: Inoue Kaoru , Yoshida Midori , Takahashi Miwa , Fujimoto Hitoshi , Shibutani Makoto , Hirose Masao , Nishikawa Akiyoshi
Published: September 2009

Madder color (MC), a food coloring extracted from roots of Rubia tinctorum L., has been proven to exert carcinogenicity in the rat kidney and liver. Furthermore, it induces DNA adducts in the kidney, liver, and colon. MC is in fact composed of anthraquinones such as lucidin‐3‐O‐primeveroside and alizarin. To clarify which of these might be responsible for the carcinogenicity, a rat medium‐term multi‐organ carcinogenesis bioassay was performed focusing on the kidney, liver, and colon. Male 6‐week‐old F344 rats after receiving five different carcinogens were fed a diet containing either 0.008% or 0.04% of alizarin or rubiadin, a metabolite of lucidin‐3‐O‐primeveroside, for 23 weeks. Treatment with 0.04% rubiadin significantly increased atypical renal tubules/hyperplasias and induced renal cell adenomas and carcinomas. Renal cell tumors were also increased with 0.04% alizarin, although at lower incidence than with rubiadin. In addition, glutathione S‐transferase placental form‐positive liver cell foci and large intestinal dysplasias were significantly increased with 0.04% rubiadin. These results indicate that both rubiadin and alizarin can increase renal preneoplastic lesions, the potential of the latter being weaker. Rubiadin may also target the liver and large intestine, suggesting a major role in madder color‐induced carcinogenicity. (Cancer Sci 2009; 100: 2261–2267)
E7050: A dual c‐Met and VEGFR‐2 tyrosine kinase inhibitor promotes tumor regression and prolongs survival in mouse xenograft models
Authors: Nakagawa Takayuki , Tohyama Osamu , Yamaguchi Atsumi , Matsushima Tomohiro , Takahashi Keiko , Funasaka Setsuo , Shirotori Shuji , Asada Makoto , Obaishi Hiroshi
Published: September 2009

c‐Met is the cellular receptor for hepatocyte growth factor (HGF) and is known to be dysregulated in various types of human cancers. Activation of the HGF/c‐Met pathway causes tumor progression, invasion, and metastasis. Vascular endothelial growth factor (VEGF) is also known as a key molecule in tumor progression through the induction of tumor angiogenesis. Because of their key roles in tumor progression, these pathways provide attractive targets for therapeutic intervention. We have generated a novel, orally active, small molecule compound, E7050, which inhibits both c‐Met and vascular endothelial growth factor receptor (VEGFR)‐2. In vitro studies indicate that E7050 potently inhibits phosphorylation of both c‐Met and VEGFR‐2. E7050 also potently represses the growth of both c‐met amplified tumor cells and endothelial cells stimulated with either HGF or VEGF. In vivo studies using E7050 showed inhibition of the phosphorylation of c‐Met and VEGFR‐2 in tumors, and strong inhibition of tumor growth and tumor angiogenesis in xenograft models. Treatment of some tumor lines containing c‐met amplifications with high doses of E7050 (50–200 mg/kg) induced tumor regression and disappearance. In a peritoneal dissemination model, E7050 showed an antitumor effect against peritoneal tumors as well as a significant prolongation of lifespan in treated mice. Our results indicate that E7050 is a potent inhibitor of c‐Met and VEGFR‐2 and has therapeutic potential for the treatment of cancer. (Cancer Sci 2009)
An analysis of renal dysfunction in 1511 patients with fractured neck of femur: the implications for peri‐operative analgesia
Authors: White S. M. , Rashid N. , Chakladar A.
Published: September 2009

Following two deaths from respiratory failure secondary to opioid toxicity in patients admitted for surgical repair of fractured neck of femur, we retrospectively studied the serum urea and electrolyte concentrations of 1511 consecutive patients requiring surgery for proximal femoral fracture, and calculated their glomerular filtration rate. Five hundred and forty‐five (36.1%) patients had renal dysfunction on admission (glomerular filtration rate < 60 ml.min−1.1.73 m−2); 435 (28.8%) had grade 3 chronic kidney disease (moderate; glomerular filtration rate 30–59 ml.min−1.1.73 m−2), 82 (5.4%) had grade 4 disease (severe; glomerular filtration rate 15–29 ml.min−1.1.73 m−2) and 28 (1.9%) had grade 5 (renal failure; glomerular filtration rate < 15 ml min−1.1.73 m−2). The 30‐day mortality for patients with renal dysfunction (62/536; 11.6%) was significantly greater (p = 0.004) than for patients with normal renal function (68/958; 7.1%), although median (IQR [range]) postoperative lengths of stay were similar 15 (10–22 [1–125]) vs 14 (9–22 [1–120]) days respectively; p = 0.06). Renal impairment is common in patients admitted for fixation of fractured neck of femur, who are consequently at risk of opioid toxicity.
A comparison of the i‐gel™ with the LMA‐Unique™ in non‐paralysed anaesthetised adult patients
Authors: Francksen H. , Renner J. , Hanss R. , Scholz J. , Doerges V. , Bein B.
Published: September 2009

This study assessed two disposable devices; the newly developed supraglottic airway device i‐gel™ and the LMA‐Unique™ in routine clinical practice. Eighty patients (ASA 1–3) undergoing minor routine gynaecologic surgery were randomly allocated to have an i‐gel (n = 40) or LMA‐Unique (n = 40) inserted. Oxygen saturation, end‐tidal carbon dioxide, tidal volume and peak airway pressure were recorded, as well as time of insertion, airway leak pressure, postoperative sore‐throat, dysphonia and dysphagia for each device. Time of insertion was comparable with the i‐gel and LMA‐Unique. There was no failure in the i‐gel group and one failure in the LMA‐Unique group. Ventilation and oxygenation were similar between devices. Mean airway pressure was comparable with both devices, whereas airway leak pressure was significantly higher (p < 0.0001) in the i‐gel group (mean 29 cmH2O, range 24–40) compared with the LMA‐Unique group (mean 18 cmH2O, range 6–30). Fibreoptic score of the position of the devices was significantly better in the i‐gel group. Post‐operative sore‐throat and dysphagia were comparable with both devices. Both devices appeared to be simple alternatives to secure the airway. Significantly higher airway leak pressure suggests that the i‐gel may be advantageous in this respect.
Randomised comparison of Pentax AirwayScope and Glidescope for tracheal intubation in patients with normal airway anatomy
Authors: Teoh W. H. L. , Shah M. K. , Sia A. T. H.
Published: September 2009

We compared intubating characteristics of the Pentax AirwayScope and Glidescope in a randomised controlled trial involving 140 patients. We found significantly shorter intubation times with mean (SD) 21.3 (12.3) vs 30.2 (13.2) s, lower intubating difficulty scores 4.4 (10.4) vs 12.8 (16.3) p < 0.001, and better grade 1 laryngeal views with the Pentax AirwayScope (95.7 vs 81.4%, p = 0.015). Significantly more optimisation manoeuvres were needed to successfully intubate with the Glidescope, with significant inability to align the tip of the tracheal tube with the glottic opening with the Glidescope in 9 (13%) vs no patients, p = 0.013. There was more mucosal bleeding (4 (5.7%) vs 1 (1.4%), p = 0.366), more lip bleeding (3 (4.3%) vs 1 (1.4%), p = 0.620) and significantly more postoperative sorethroat, 13 (18.6%) vs 0, p < 0.001 associated with the Glidescope.
Global oximetry: an international anaesthesia quality improvement project
Authors: Walker I. A. , Merry A. F. , Wilson I. H. , McHugh G. A. , O’Sullivan E. , Thoms G. M. , Nuevo F. , Whitaker D. K. ,   on behalf of the GO Project teams
Published: September 2009

Pulse oximetry is mandatory during anaesthesia in many countries, a standard endorsed by the World Health Organization ‘Safe Surgery Saves Lives’ initiative. The Association of Anaesthetists of Great Britain and Ireland, the World Federation of Societies of Anaesthesiologists and GE Healthcare collaborated in a quality improvement project over a 15‐month period to investigate pulse oximetry in four pilot sites in Uganda, Vietnam, India and the Philippines, using 84 donated pulse oximeters. A substantial gap in oximeter provision was demonstrated at the start of the project. Formal training was essential for oximeter‐naïve practitioners. After introduction of oximeters, logbook data were collected from over 8000 anaesthetics, and responses to desaturation were judged appropriate. Anaesthesia providers believed pulse oximeters were essential for patient safety and defined characteristics of the ideal oximeter for their setting. Robust systems for supply and maintenance of low‐cost oximeters are required for sustained uptake of pulse oximetry in low‐ and middle‐income countries.
Depletion of CD4+CD25+ regulatory T cells enhances natural killer T cell-mediated anti-tumour immunity in a murine mammary breast cancer model
Authors: Hong H , Gu Y , Zhang H , Simon A K , Chen X , Wu C , Xu X-N , Jiang S
Published: September 2009

Both invariant natural killer T (NK T) cells and CD4+CD25+ T regulatory cells (Tregs) regulate the immune system to maintain homeostasis. In a tumour setting, NK T cells activated by α-galactosylceramide (α-GalCer) execute anti-tumour activity by secreting cytokines. By contrast, Tregs intrinsically suppress antigen-specific immune responses and are often found to be elevated in tumour patients. In this study, we have shown that Tregs regulate NK T cell function negatively in vitro, suggesting a direct interaction between these cell types. In a murine mammary tumour model, we demonstrated that administration of either α-GalCer or anti-CD25 antibody alone markedly suppressed tumour formation and pulmonary metastasis, and resulted in an increase in the survival rate up to 44% (from a baseline of 0%). When treatments were combined, depletion of Tregs boosted the anti-tumour effect of α-GalCer, and the survival rate jumped to 85%. Our results imply a potential application of combining Treg cell depletion with α-GalCer to stimulate NK T cells for cancer therapy.
Alpha versus beta: are we on the way to resolve the mystery as to which is the endogenous ligand for natural killer T cells?
Authors: Ilan Y
Published: September 2009

Natural killer T (NKT) lymphocytes are a unique subset of cells that play a role in regulating the immune system. For the past decade, studies have focused upon attempts to define these cells and to determine the ligand(s) that are required for their development and peripheral activation. Many research groups have focused upon determining the mechanisms for activating or inhibiting NKT cells in an attempt to control immune-mediated disorders as well as infectious and malignant conditions by using different ligand structures. Alpha-anomeric glycolipids and phospholipids derived from mammalian, bacterial, protozoan and plant species have been suggested as potential ligands for these lymphocytes. Some of these ligands were structured in forms that can bind to CD1d molecules. The lack of alpha-anomeric glycosphingolipids in mammals and the modest effect of these ligands in human studies, along with recent data from animal models and humans on the NKT-dependent immunomodulatory effect of beta-glycosphingolipids, suggest that the beta-anomeric ligands have the potential to be the endogenous NKT ligand.
Presentation and comments on EU legislation related to food industries–environment interactions: organic contaminants (chemicals, pesticides, dioxins, furans, biocides and their waste management)
Authors: Arvanitoyannis Ioannis S. , Tserkezou Persefoni , Choreftaki Stefania
Published: September 2009

The first part of this review on European Union (EU) legislation related to food industries–environment interactions deals with chemicals which, in their majority, make their way to food. Such substances are the pesticides and fertilizers the residues of which abound in many agricultural produces (both of plant or animal origin). Another crucial issue is the unintentional release of dioxins and furans through combustion. Detergents or sanitizers in conjunction with compounds considered hazardous or corrosive or flammable stand for other topics falling in the general category of chemicals employed in the food industry. The aim of this review is to cover all the current EU legislation in the field of chemicals (dioxins, furans, pesticides, biocides products, fertilizers, sanitizers) coming directly or indirectly in contact with food and their waste management by providing six comprehensive and easy‐to‐use tables, and a synopsis of the main points of the currently in force EU legislation.
Periodontal and microbiological parameters in children and adolescents with cleft lip and /or palate
Authors: PERDIKOGIANNI HARIKLIA , PAPAIOANNOU WILLIAM , NAKOU MELACHRINI , OULIS CONSTANTINE , PAPAGIANNOULIS LIZA
Published: September 2009

Objective.  To evaluate the oral hygiene and the periodontal condition of children and adolescents with cleft lip and/or palate (CLP).

Methods.  Forty‐one children and adolescents, 4–18 years, with CLP and 41 normal controls participated. Clinical parameters examined were the plaque and gingival index and Community Periodontal Index of Treatment Needs. For teeth in the cleft area, probing pocket depth, bleeding on probing, and tooth mobility were also evaluated. Samples of subgingival plaque were collected from 21 randomly selected patients of each group.

Results.  The CLP group had generally poorer oral hygiene (plaque index significantly higher) compared with the control. Children in both groups presented mild degree of gingivitis. Teeth in the cleft area had significantly higher pocket probing depth and tooth mobility, compared with corresponding teeth in the control group. The microbial analysis did not reveal significant differences in the composition of the subgingival microbiota between groups. Teeth in the cleft presented higher isolation frequencies and mean percentages of periodontopathic bacteria.

Conclusion.  Youngsters with CLP showed poor oral hygiene and worse periodontal condition, compared with controls. The above results advocate their participation in an intensive preventive dental programme that should start at an early age, possibly decreasing the risk of future periodontal disease.
Positive interactions can increase size inequality in plant populations
Authors: Chu Cheng‐Jin , Weiner Jacob , Maestre Fernando T. , Xiao Sa , Wang You‐Shi , Li Qi , Yuan Jian‐Li , Zhao Lu‐Qiang , Ren Zheng‐Wei , Wang Gang
Published: September 2009

1. Large variation in the size of individuals is a ubiquitous feature of natural plant populations. While the role of competition in generating this variation has been studied extensively, the potential effects of positive interactions among plants, which are common in high‐stress environments, have not been investigated.

2. Using an individual‐based ‘zone‐of‐influence’ model, we investigate the effects of competition, abiotic stress and facilitation on size inequality in plant monocultures. In the model, stress reduces the growth rate of plants, and facilitation ameliorates the effects of stress. Both facilitation and competition occur in overlapping zones of influence. We tested some of the model’s predictions with a field experiment using the clonal grass Elymus nutans in an alpine meadow.

3. Facilitation increased the size inequality of model populations when there was no density‐dependent mortality. This effect decreased with density as competition overwhelmed facilitation. The lowest size inequality was found at intermediate densities both with the model and in the field.

4. When density‐dependent mortality was included in the model, stress delayed its onset and reduced its rate by reducing growth rates, so the number of survivors at any point in time was higher under harsh than under more benign conditions. Facilitation increased size inequality during self‐thinning.

5. Synthesis. Our results demonstrate that facilitation interacts with abiotic stress and competition to influence the degree of size inequality in plant populations. Facilitation increased size inequality at low to intermediate densities and during self‐thinning.
Regulation of putative methyl‐sulphide methyltransferases in Methanosarcina acetivorans C2A
Authors: Bose Arpita , Kulkarni Gargi , Metcalf William W.
Published: September 2009

The regulation of the Methanosarcina acetivorans mtsD, mtsF and mtsH genes, which encode putative corrinoid/methyltransferase isozymes involved in methylsulphide metabolism, was examined by a variety of methods, suggesting that their expression is regulated at both the transcriptional and post‐transcriptional levels. Transcripts of all three genes, measured by quantitative reverse transcription PCR, were shown to be most abundant during growth on methanol with dimethylsulphide (DMS). Transcript levels were also high in media with CO or methylamines, but much lower with methanol. In contrast, translational fusions to mtsD showed high expression levels on CO or methanol with DMS, while the mtsF translational fusion showed highest reporter gene activity on methylamines with much lower expression on CO or methanol with DMS. The activity of mtsD and mtsF fusions was very low when the strains were grown in methanol or acetate. Expression of the mtsH fusion was not detected on any substrate, despite the presence of an mRNA transcript. The transcription start sites of all three genes were determined by 5′‐RACE revealing large leader sequences for each transcript. Characterization of deletion mutants lacking putative regulatory genes suggests that MA0862 (msrF), MA4383 (msrC) and MA4560 (msrG) act as transcriptional activators of mtsD, mtsF and mtsH respectively.
N‐ and C‐terminal regions of the quorum‐sensing activator TraR cooperate in interactions with the alpha and sigma‐70 components of RNA polymerase
Authors: Qin Yinping , Keenan Carrie , Farrand Stephen K.
Published: September 2009

Positive control (PC) mutants defining 20 residues of the quorum‐sensing activator TraR were isolated that bind DNA but show defects in activating transcription from class I, class II or both types of promoters. These PC residues, located in both the N‐ and C‐terminal regions, combine to form three patches, one on the top (II) and two near the DNA binding domain on both lateral faces of the dimer (I and III). Patches I and II, but not patch III, involve residues from both protomers and are essential for activation. TraR‐mediated activation in Escherichia coli requires expression of the α‐subunit of Agrobacterium (αAt). We report that TraR also activates a class II promoter in E. coli when coexpressed with σ70At. Analyses in E. coli expressing αAt, σ70At or both subunits indicate that most of the PC residues are important for interactions with αAt and that these interactions are predominant for activation of class II promoters. Using the E. coli system we identified nine residues in the C‐terminal domain of αAt that are required for stimulating TraR‐mediated activation. We conclude that N‐ and C‐terminal residues of TraR from both protomers cooperate to define regions of the protein important for interactions with RNAP.
Regulatory RNAs in prokaryotes: here, there and everywhere
Authors: Narberhaus Franz , Vogel Jörg
Published: September 2009

A recent meeting on ‘Regulatory RNAs in prokaryotes’ reflected the growing interest in this research topic. Almost 200 scientists met to discuss the identification, structure, function and mechanistic details of regulatory RNAs in bacteria and archaea. The topics included small regulatory RNAs, riboswitches, RNA thermosensors and CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) elements.
Interaction of FliK with the bacterial flagellar hook is required for efficient export specificity switching
Authors: Minamino Tohru , Moriya Nao , Hirano Takanori , Hughes Kelly T. , Namba Keiichi
Published: September 2009

FliK–FlhB interaction switches export specificity of the bacterial flagellar protein export apparatus to stop hook protein export at an appropriate timing for hook length control. The hook structure is required for the productive FliK–FlhB interaction to flip the switch but it remains unknown how it works. Here, we characterize the role of FliK in the switching probability in the absence of the hook. When RflH/Flk was missing in the hook mutants, the switching occurred at a low probability. Overproduction of FliK significantly increased the switching probability although not at the wild‐type level. An in‐frame deletion of residues 129 through 159 of FliK weakened the interaction with the hook protein but not with the hook‐capping protein, producing polyhooks with filaments attached. We suggest that temporary association of FliK with the inner surface of the hook during FliK secretion results in a pause in the secretion process to allow the C‐terminal switch domain of FliK to be positioned and appropriately oriented near FlhB for catalysing the switch and that RflH/Flk interferes with premature switch by preventing access of cytoplasmic FliK to FlhB and even that of FliK during its secretion until hook length reaches 55 nm; only then FliKC passes the RflH/Flk block.