bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeted inhibition of mammalian target of rapamycin for the treatment of advanced renal cell carcinoma
Authors: Kapoor Anil , Figlin Robert A.
Published: May 2009

Clinical trials have validated the importance of mammalian target of rapamycin (mTOR) as a targeted mechanism in the treatment of renal cell carcinoma (RCC). Temsirolimus, an mTOR inhibitor that is approved for treatment of advanced RCC, has demonstrated both overall survival benefits and progression‐free survival benefits versus interferon‒α as first‐line treatment for patients with poor prognostic features. Exploratory subset analyses indicated that temsirolimus benefits patients with RCC regardless of tumor histology or nephrectomy status. Everolimus, the second mTOR inhibitor to demonstrate activity in RCC, improved progression‐free survival versus placebo in patients whose disease progressed after treatment with vascular endothelial growth factor receptor tyrosine kinase inhibitors (sunitinib, sorafenib, or both); benefit was observed for all risk groups. Deforolimus also exhibited antitumor activity against RCC in early clinical studies. There is now compelling clinical evidence for the effectiveness of targeting mTOR in the treatment of RCC. Cancer 2009. © 2009 American Cancer Society.
Increased vascular endothelial growth factor expression, CD3‐positive cell infiltration, and oxidative stress in premalignant lesions of the cervix
Authors: Carrero Yenddy , Callejas Diana , Alaña Freddy , Silva Chiquinquirá , Mindiola Raimy , Mosquera Jesús
Published: May 2009

BACKGROUND:

Vascular endothelial growth factor (VEGF) plays an important role in cervical intraepithelial neoplasia (CIN) progression. The occurrence of leukocytes has been documented in CIN; however, their role in VEGF production remains unknown. Oxidative stress has been involved in the progression of malignant neoplasias, but to the authors' knowledge tissue oxidative stress in CIN has not been documented. The objective of the current study was to investigate the expression of VEGF, leukocyte infiltration, leukocyte VEGF expression, and nitrogen/oxygen metabolism in cervical tissues from patients with CIN.

METHODS:

Indirect immunofluorescence was used to study the expression of VEGF and leukocyte infiltration in cervical samples from 55 patients with CIN and 7 normal controls. Superoxide anion (O2−) expression was determined by a cytochemical method, and tissue and serum nitric oxide by the Griess reaction. Human papillomavirus (HPV) DNA and HPV types were identified by the hybrid capture 2 HPV DNA test.

RESULTS:

Increased expression of VEGF was observed related to the progression of CIN. A significant increment of CD3 lymphocytes was found in CIN type 3 (CIN 3) and coexpression of CD3/VEGF and monocyte‐macrophage/VEGF in CIN 2 and 3. Increased O2−‐positive cells were found in CIN 2 and 3; however, tissue nitrate‐nitrite content remained similar to controls. The incidence of HPV infection was 16% in patients with CIN. No significant differences were observed in the values of HPV‐positive or HPV‐negative patients.

CONCLUSIONS:

Different factors leading to cervical neoplasia progression may be involved in the evolution of CIN, and the presence of these factors is most likely not related to the HPV infection status. Cancer 2009. © 2009 American Cancer Society.
Network numerical modelling of unsteady MHD‐free convection flow with mass transfer, hall current and viscous dissipation effects
Authors: Zueco Joaquín , Eguía P. , Patiño D. , López‐Ochoa L. M.
Published: May 2009

The transient problem of the coupled heat and mass transfer of an electrically conducting fluid in magnetohydrodynamic‐free convection from a semi‐infinite plate, with viscous dissipation and the Hall currents taken into account, is studied. The induced magnetic field due to the motion of the electrically conducting fluid is negligible. The non‐dimensional governing equations for the problem are solved by means of a numerical technique based on the electric analogy (Network Simulation Method). This method provides the numerical response of the system by running the network on circuit resolution software, providing the solution for both transient and steady‐state problems at the same time. Programming does not require manipulation of the sophisticated mathematical software that is inherent in other numerical methods. Numerical results for the velocities, temperature and concentration profiles are presented graphically for different values of the magnetic field parameter, the Hall parameter, and the Eckert, Schmidt, Grashof and modified Grashof numbers. Copyright © 2009 John Wiley & Sons, Ltd.
Towards computational modelling of aortic stenosis
Authors: van Loon R.
Published: May 2009

In this paper fluid–structure interaction models of bioprosthetic or native aortic valves are proposed for the assessment of aortic stenosis severity. The fictitious domain approach is applied for the blood–valve interaction and the valve and root geometry are defined such that geometrical changes can easily be made. Clinically relevant scenarios are demonstrated using the models by introducing variable stroke volumes, differently shaped valve and root, leaflet fusion or calcifications. Systolic behaviour of the valves is observed and the severity of the occlusions is evaluated using the following clinically relevant criteria: geometrical orifice area, trans‐valvular pressure gradient, effective orifice area and Energy loss coefficient. Within this context, the benefits, shortcomings and potential of the presented three‐dimensional models are identified and discussed. Copyright © 2009 John Wiley & Sons, Ltd.
Force Spectroscopy of the Interaction Between Mycobacterial Adhesins and Heparan Sulphate Proteoglycan Receptors
Authors: Dupres Vincent , Verbelen Claire , Raze Dominique , Lafont Frank , Dufrêne Yves F.
Published: May 2009

New avenues in pathogenesis research: Single‐molecule measurements using AFM elucidate the specific binding forces between pathogen–host interactions. A bacterial adhesin (HBHA) on the AFM tip detects single HSPG receptors directly on living host cells (see figure). In vivo HBHA‐HSPG binding forces are similar to those measured in vitro for HBHA‐heparin complexes.

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Understanding the molecular interactions between bacterial adhesion proteins (adhesins) and their receptors is essential for elucidating the molecular mechanisms of bacterial pathogenesis. Here, atomic force microscopy (AFM) is used to explore the specific interactions between the heparin‐binding hemagglutinin (HBHA) from Mycobacterium tuberculosis, and heparan sulphate proteoglycan (HSPG) receptors on live A549 pneumocytes. First, we show that the specific binding forces between single HBHA‐HSPG pairs, 57±16 pN, are similar to the forces measured earlier between HBHA and heparin molecules. Second, we mapped the distribution of single HSPG receptors on the surface of A549 cells, revealing that the proteins are widely and homogeneously exposed. Third, we observed force curves with constant force plateaus at large pulling velocities, reflecting the extraction of membrane tethers or nanotubes. These single‐molecule measurements provide new avenues in pathogenesis research, particularly for elucidating the molecular basis of pathogen–host interactions.
Impaired decentration in personality disorder: A series of single cases analysed with the metacognition assessment scale
Authors: Dimaggio Giancarlo , Carcione Antonino , Nicolò Giuseppe , Conti Laura , Fiore Donatella , Pedone Roberto , Popolo Raffaele , Procacci Michele , Semerari Antonio
Published: May 2009

Background: There is growing support for the idea that an impaired understanding of others' mental states is an underlying feature of personality disorder (PD). Only recently has there begun to be evidence of impairments to subjects' ability to infer and reason about others' intentions and emotions, and detach from their own perspective when doing so. Method: We analysed the transcripts from the first 16 psychotherapy sessions of 14 PD patients. Scales for understanding others' minds from the Metacognition Assessment Scale were used. Results: Patients were generally able to describe others' mental states, although, at times, they had problems. There was, on the other hand, an inability to decentre while reasoning about others, and this was common to all the patients. Conclusions: PDs indeed feature a poor decentration, which is not easily identified with the usual lab tasks. Implications for further research and treatment are discussed. Copyright © 2009 John Wiley & Sons, Ltd.

Key Practitioner Message:

• Patients with personality disorders have substantial difficulties in adopting others' point of view and standing back from their own, and grasping that they are not the center of other peoples' thoughts.
A Direct Route to Bifunctional Aldehyde Derivatives via Self‐ and Cross‐Metathesis of Unsaturated Aldehydes
Authors: Miao Xiaowei , Fischmeister Cédric , Bruneau Christian , Dixneuf Pierre H.
Published: May 2009

Ruthenium‐catalyzed self‐ and cross‐metathesis, with acrolein, acrylonitrile, acrylic acid and methylacrylate, of the bioresource undecylenic aldehyde leads to a variety of unsaturated ω‐functional aldehydes. Tandem olefin metathesis/hydrogenation catalytic reactions afford saturated C20 and C12 diols in good yields.

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Esterification of Acidic Oils over a Versatile Amorphous Solid Catalyst
Authors: Zaccheria Federica , Brini Simona , Psaro Rinaldo , Scotti Nicola , Ravasio Nicoletta
Published: May 2009

An amorphous SiO2–ZrO2 catalyst shows high activity in the esterification of free fatty acids contained in vegetable oils while at the same time promoting the transesterification of triglycerides. The catalyst is hence a good candidate for a low‐waste deacidification pretreatment or for a one‐pot biodiesel production process starting from oils with a high acid content.

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Dynamics of Dislocations in a 2D Plasma Crystal
Authors: Nosenko V. , Zhdanov S. K.
Published: May 2009

Recent experimental results on the dislocation dynamics in a two‐dimensional plasma crystal are reviewed. A single layer of micron‐size microspheres was suspended in the sheath of a capacitively coupled rf discharge. The particles self‐organized in a triangular lattice. Edge dislocations were created in pairs in this plasma crystal when the internal shear stress built up above a threshold, due to the crystal's slow differential rotation. Basic stages of dislocation nucleation were identified and studied, from gradual pile‐up of shear strain in the crystal to eventual escape of free dislocations. After nucleation, dislocations moved supersonically with respect to the shear waves and generated shear‐wave Mach cones (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Modelling of Voids in Complex Radio Frequency Plasmas
Authors: Goedheer W.J. , Land V. , Venema J.
Published: May 2009

In this paper hydrodynamic and kinetic approaches to model low pressure capacitively coupled complex radiofrequency discharges are discussed and applied to discharges under microgravity. Experiments in the PKE‐Nefedov reactor on board the International Space Station, as well as discharges in which gravity is compensated by means of thermophoresis are simulated with a 2‐D cylindrically symmetric hydrodynamic model. Kinetic effects are studied with a 1‐D Particle‐In‐Cell plus Monte Carlo model in which capture and scattering by dust grains is included. Simulations with this model address non‐local effects and modulated discharges (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Dynamical Heterogeneities in 2D Dusty Plasma Liquids at the Discrete Level
Authors: Chan Chia‐Ling , Io Chong‐Wai , I Lin
Published: May 2009

Down to the discrete microscopic level, the liquid is neither homogeneous nor completely disordered. The interplay of mutual coupling and thermal agitation makes the system support short range structural order, and avalanche‐type cooperative hopping excitations which lead to structural arrangement. The rich dynamical behaviors of spatio‐temporal heterogeneities are still poorly understood because of the lack of proper tools for direct visualization. The dusty plasma liquid can be self‐organized by negatively charged micrometer sized dusts suspending in a low‐pressure rf discharge background. Its sub‐mm inter‐particle distance and the tens of second thermal relaxation time make it a proper system to mimic and understand the generic spatio‐temporal behaviors of the liquid at the discrete kinetic level through direct optical video‐microscopy. In this paper, we briefly review the recent studies on the dynamical heterogeneities of the cold 2D dusty plasma liquids at the discrete level. The effects of mutual interaction, thermal agitation, external shear, and tight confinement on micro‐motion, anomalous diffusion, avalanche‐type excitations of hopping clusters and defect clusters, structural ordering and rearrangement, and visco‐elastic responses are presented and discussed (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Dust Particle Alignments in a Plasma Sheath
Authors: Samarian A. A. , Vladimirov S. V.
Published: May 2009

Stability of vertical and horizontal arrangement of dust particles levitating in an rf sheath are discussed. Disruptions of particle arrangements are triggered by changing the discharge controlling parameters (pressure and peak‐to‐peak voltage) as well as by applying an additional bias to the confining electrode or by a laser beam. It is established that the most important controlling parameter is the relative strength of the horizontal and the vertical confinements. The clear hysteretic phenomena are observed for the horizontal‐vertical‐horizontal transition cycle. This hysteretic behavior can be attributed to the stabilizing (for the vertical alignment) and destabilizing (for the horizontal alignment) influence of the plasma wake potential. The width of the hysteresis increases with decreasing pressure thus indicating on stronger influence of the wake phenomena for low pressures. The horizontal alignment instability at the critical confinement can provide a new diagnostic tool for determining the wake parameters (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Towards a Microscopic Theory of Particle Charging
Authors: Bronold F. X. , Fehske H. , Kersten H. , Deutsch H.
Published: May 2009

We recently questioned the treatment of a dust particle as a perfect absorber for electrons and ions and proposed a surface model for the charge of a dust particle in a quiescent plasma which combines the microscopic physics at the grain boundary (sticking into and desorption from external surface states) with the macrophysics of the discharge (plasma collection fluxes). Within this model the charge and partial screening of the particle can be calculated without relying on the condition that the total electron collection flux balances on the grain surface the total ion collection flux. Grain charges obtained from our approach compared favorably with experimental data. The purpose of this paper is to describe our model in more detail, in particular, the hypotheses on which it is built, contrast it with the standard charging models based on flux balancing on the grain surface, and to analyze additional experimental data (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Dust Clouds in Dc‐Generated Dusty Plasmas: Transport, Waves, and Three‐Dimensional Effects
Authors: Thomas E.
Published: May 2009

The study of dusty plasmas in dc‐generated plasmas is a broad topic because of the wide variety of experimental configurations that fall under the category of “dc plasma source”. Experimental configurations such as the hot filament discharge, anodic (anode/cathode) discharge, and Q‐machine are all variations of the “dc plasma source” in which extensive studies of dusty plasmas have been performed. This paper will review dusty plasma investigations in these plasma sources. First, an introduction to each of these configurations and representative examples of each one will be given. This will be followed by a discussion of microparticle confinement in each of these configurations. Then, key results from dusty plasma investigations using these devices will be discussed. Specific emphasis will be placed on studies of: microparticle charging, particle cloud morphology, dust‐driven and dust‐modified waves, and strongly coupled effects. Some remarks on emerging research areas will be given at the end (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Growth Process of Polyaniline Thin Films Formed by Hot Wire CVD
Authors: Zaharias Gillian A. , Bent Stacey F.
Published: May 2009

We explore the use of hot‐wire (HW) CVD as an alternative, solvent‐free technique to produce compact films similar to conventional polyaniline. Film deposition and molecular bonding are studied as functions of Ta filament temperature, aniline pressure, and substrate temperature to allow an insight into the film growth mechanism, which is postulated to depend largely on reactions of aniline with H and C atoms generated at the hot wire. The process gas, aniline, is found to cause rapid formation of tantalum carbide and carbon deposits on the hot Ta surface. The accompanying change in film quality as the filament ages is studied.
Correlation of flow cytometrically determined expression of ZAP‐70 using the SBZAP antibody with IgVH mutation status and cytogenetics in 1,229 patients with chronic lymphocytic leukemia
Authors: Kern Wolfgang , Dicker Frank , Schnittger Susanne , Haferlach Claudia , Haferlach Torsten
Published: May 2009

Background:

ZAP‐70 provides an important prognostic information in chronic lymphocytic leukemia (CLL); however, the most appropriate antibody clone and way of analysis have not yet been defined.

Methods:

We determined ZAP‐70 expression in 1,229 patients with CLL using the SBZAP clone by applying three different ways of analysis (% positive B‐cells, mean fluorescence intensity (MFI) in B‐cells, MFI ratio T‐cells:B‐cells).

Results:

ZAP‐70 expression was related to somatic hypermutation status of IgVH genes for all three ways of analysis (P < 0.0001 each). The strongest correlation was found for MFI ratio (r = −0.475, P < 0.0001); cases with mutated and unmutated IgVH status significantly differed in their mean MFI ratio (6.33 vs. 3.34, P < 0.0001). ZAP‐70 expression was weaker in sole del(13q) (5.44 vs. 4.44, P = 0.001) and stronger in del(11q) (3.31 vs. 5.29, P < 0.0001) and del(6q) (3.29 vs. 5.18, P = 0.005). MFI ratio was significantly related to time to therapy (P = 0.004, RR = 0.79) in 221 evaluable cases. Multivariate analysis proved MFI ratio (P = 0.043, RR = 0.64) and CD38 (P = 0.047, RR = 1.20 per 10%) as only parameters independently related to time to therapy.

Conclusions:

Determination of ZAP‐70 expression using SBZAP and applying MFI ratio T‐cells:B‐cells results in significant relations to IgVH mutation status, cytogenetics, and outcome and should be further analyzed and considered for routine application in CLL. © 2009 Clinical Cytometry Society
A network processor‐based architecture for multi‐gigabit traffic analysis
Authors: Di Pietro A. , Ficara D. , Giordano S. , Oppedisano F. , Procissi G. , Vitucci F.
Published: May 2009

The wide availability of cheap and effective commodity PC hardware has driven the development of versatile traffic monitoring software such as protocol analyzers, traffic characterizers and intrusion detection systems. Most of them are designed to run on general purpose architectures and are based on the well‐known libpcap API, which has rapidly become a de facto standard. Although many improvements have been applied to packet capturing software, it still suffers from several performance flaws, mainly due to the underlying hardware bottlenecks. To overcome these issues, this paper proposes a system architecture, which combines the high performance of a Network Processor card with the flexibility of software‐based solutions. It allows for removing most part of the hardware limitations exhibited by a purely PC‐based architecture, while preserving the full compliance to any software applications based on libpcap. In addition, the proposed system enables the use of monitoring applications at the wire speed, with the possibility of on‐the‐fly data processing. The system performance has been thoroughly assessed: the results show that it clearly outperforms the previous PC‐based solutions in terms of packet capturing power, while the timestamping accuracy is as good as that achieved by DAG cards. Copyright © 2009 John Wiley & Sons, Ltd.
Dopamine modulation of the In vivo acetylcholine response in the Drosophila mushroom body
Authors: Tsydzik Vitold , Wright Nicholas J.D.
Published: May 2009

Olfactory sensory information in Drosophila is transmitted through antennal lobe projections to Mushroom Body neurons (Kenyon cells) by means of cholinergic synapses. Application of acetylcholine (ACh) and odors produce significant increases in intracellular calcium ([Ca2+]i) in these neurons. Behavioral studies show that Kenyon cell activity is modulated by dopaminergic inputs and this modulation is thought to be the basis for an olfactory conditioned response. However, quantitative assessment of the synaptic inputs to Kenyon cells is currently lacking. To assess neuronal activity under in vivo conditions, we have used the endogenously‐expressed camgaroo reporter to measure [Ca2+]i in these neurons. We report here the dose‐response relationship of Kenyon cells for ACh and dopamine (DA). Importantly, we also show that simultaneous application of ACh and DA results in a significant decrease in the response to ACh alone. In addition, we show inhibition of the ACh response by cyclic adenosine monophosphate. This is the first quantitative assessment of the effects of these two important transmitters in this system, and it provides an important basis for future analysis of the cellular mechanisms of this well established model for associative olfactory learning. © 2009 Wiley Periodicals, Inc. Develop Neurobiol, 2009
Identification of novel genes involved in the development of the sword and gonopodium in swordtail fish
Authors: Offen Nils , Meyer Axel , Begemann Gerrit
Published: May 2009

Male swordtail fish of the genus Xiphophorus develop a sword, a colourful extension of the caudal fin, that evolved by sexual selection through female choice. Swords and gonopodia, an intromittent organ developing from the male anal fin, can be prematurely induced by exogenous testosterone, offering the opportunity to examine the identity and expression profiles of genes required during various stages of fin metamorphosis. Here, we employed suppression subtractive hybridisation to identify genes specifically up‐regulated during two early stages of sword and gonopodium development. We identified 128 different sequences with significant similarity to known genes and characterized the rack1, dusp1, klf2, and tmsβ‐like genes as specifically up‐regulated in developing as well as regenerating fin rays of the sword and gonopodium. We show that some of these genes follow distinct expression profiles in swords and gonopodia, suggesting differences in the genetic networks underlying the development of anal and caudal fin modifications. Developmental Dynamics 238:1674–1687, 2009. © 2009 Wiley‐Liss, Inc.
Windows of reflection: conceptualizing dyslexia using the social model of disability
Authors: Macdonald Stephen. J.
Published: May 2009

The aim of this study is to develop perceptual knowledge of dyslexia from adults diagnosed with this condition. Historically, the dominant conceptual frameworks used to study dyslexia stem from psychological or educational practice. These disciplines predominantly draw on professional neuro‐biological or educational knowledge that can be broadly summarized within a medical or educational model approach. Both the medical and educational models view dyslexia as resulting from a neurological and learning dysfunction. As such, only a small amount of research has attempted to locate dyslexia within a sociological context. This paper analyses the life narratives of adults diagnosed with dyslexia using the social model of disability. The author investigates the impact that disabling barriers have in education and employment for people with dyslexia. The implications of this are discussed, particularly how issues of disabling barriers and social‐class structures affect the lives of people with dyslexia. The paper argues that social‐class positioning and institutional discrimination (in the form of disabling barriers) shape the experiences of people living with this condition. Copyright © 2009 John Wiley & Sons, Ltd.
Dielectric Constant Controlled Solvothermal Synthesis of a TiO2 Photocatalyst with Tunable Crystallinity: A Strategy for Solvent Selection
Authors: Wu Jianjun , Lü Xujie , Zhang Linlin , Huang Fuqiang , Xu Fangfang
Published: May 2009

Phase‐pure anatase TiO2 nanocrystals with a tunable crystallinity have been prepared by a one‐step solvothermal method in the absence of any templates or additives. The crystallinity can be successfully controlled by varying the dielectric constant of the reaction solvent. 2‐Propanol, which has the lowest dielectric constant of those studied, favors the crystallization of TiO2 nanocrystals with the best crystallinity, in other words nano‐TiO2 crystals with the largest crystallite size (14.8 nm), lowest lattice strain (7.27 × 10–3), and highest photocatalytic efficiency (almost six times that obtained in methanol). The effect of the dielectric constant on the solubility of the precursor and subsequent nucleation and crystal growth is discussed in detail. These discussions shed some light on solvent selection for the designed synthesis of nano‐TiO2 with different crystallinity. The photocatalytic activity of the as‐prepared samples has also been investigated with respect to their crystallinity.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
1,1′‐Disubstituted Ferrocenes with Aluminum: Dinuclear and Trinuclear Dialumina[1.1]ferrocenophanes as Pyridine Adducts
Authors: Wrackmeyer Bernd , Klimkina Elena V. , Milius Wolfgang
Published: May 2009

Ferrocenes bearing dialkylaluminum substituents in the 1,1′‐positions were characterized as their dipyridine adducts, and it was shown that they can be transformed into dinuclear alkylaluminum‐bridged [1.1]ferrocenophanes and finally into the trinuclear aluminum‐bridged ferrocenophane, both as dipyridine adducts. The synthesis of the latter compound was optimized and found to be most efficient (>40 % yield) through the reaction of 1,1′‐dilithioferrocene with MeAlCl2. The molecular structures of the dinuclear and trinuclear complexes were determined by X‐ray crystallography. The solution‐state structures of the new compounds were studied by multinuclear magnetic resonance methods, including 1H–1H NOE difference experiments.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Asymmetric Organocatalytic Cyclopropanation – Highly Stereocontrolled Synthesis of Chiral Cyclopropanes with Quaternary Stereocenters
Authors: Companyó Xavier , Alba Andrea‐Nekane , Cárdenas Francisco , Moyano Albert , Rios Ramon
Published: May 2009

A convenient and novel domino reaction for the synthesis of highly functionalized cyclopropanes is reported. The addition of 2‐bromoketo esters to a variety of α,β‐unsaturated aldehydes catalyzed by secondary amines leads to chiral cyclopropanes with three stereogenic carbon atoms, including one quaternary stereocenter, in a highly stereocontrolled fashion.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Reductive‐Cyclization‐Mediated Synthesis of Fused Polycyclic Quinolines from Baylis–Hillman Adducts of Acrylonitrile: Scope and Limitations
Authors: Singh Virender , Hutait Samiran , Batra Sanjay
Published: May 2009

The synthesis of a variety of polycyclic quinolines is described. The target molecules were obtained in two steps by an initial reductive cyclization followed by another intramolecular cyclization in the allylamines afforded from either the acetates or allyl bromides of Baylis–Hillman adducts of 2‐nitrobenzaldehydes and acrylonitrile. The two steps proceeded in one‐pot for those substrates in which a formyl or hydroxy group reacted with the amino group of the 2‐aminoquinoline in the second intramolecular cyclization. In contrast, a basic medium was necessary for the second intramolecular cyclization reaction in substrates in which an alkoxycarbonyl group and the amino group participated. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Reinvestigation of Supramolecular Complexes with Cyclophanes of the Stetter and Koga Type: Agreement and Disagreement with Solid‐State Structures
Authors: Wald Peter , Schneider Hans‐Jörg
Published: May 2009

In this paper we reinvestigate the historically oldest complexations with cyclophanes of the Stetter and Koga type (1 and 2), and new macrocycle 3, which is a hybrid of the two former. NMR titrations in aqueous solution reveal that benzene forms, as known, strong complexes with Koga‐type host 2, but also weaker ones with Stetter cyclophane 1, in contrast to earlier observations with the corresponding crystals. Tosylate forms weak complexes with 1, but stronger ones with 2 and 3. The binding free energy difference (ΔG = 7 kJ mol–1) between tosylate and benzene as guest and 2 or 3 as host agrees well with the salt bridge increment found earlier with many supramolecular complexes. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Synthesis of a β‐Ketophosphonate Bioisostere of UDP‐N‐acetylglucosamine
Authors: Auberger Nicolas , Gravier‐Pelletier Christine , Le Merrer Yves
Published: May 2009

A concise route to a new β‐ketophosphonate analog of glycosyl nucleotides is described. Such a diphosphate bioisostere is a stable mimic of enzyme substrates involved in peptidoglycan biosynthesis and will be the starting point for the development of new potential antibiotics. The synthesis is carried out by condensing a lithiomethylenephosphonate derivative on a methyl N‐acetylglucosaminylacetate followed by esterification with a uridine derivative. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Minority report: Social identity, cognitions of rejection and intergroup anxiety predicting prejudice from one racially marginalized group towards another
Authors: Barlow Fiona Kate , Louis Winnifred R. , Terry Deborah J.
Published: May 2009

The present study investigated the attitudes of one disadvantaged minority group in Australia, Asian Australians (N = 87), towards another more severely disadvantaged minority group, Aboriginal Australians. Asian Australian attitudes were compared to European Australian attitudes (N = 273). Cognitions of outgroup rejection, identification and intergroup anxiety were assessed in relation modern racism, desire for intergroup avoidance and support for a national apology. Both Asian and European participants who perceived Aboriginal Australians as rejecting were more likely to express intergroup anxiety. Anxiety mediated the relationship between cognitions of rejection and the dependent variables. Whilst there was a direct positive relationship between European Australian identification and prejudice, for Asian Australian participants, identification moderated the relationship between cognitions of rejection and the dependent variables. Highly identified Asian Australian participants were particularly sensitive to cognitions of rejection, which increased modern racism and avoidance and lowered political support. The pattern was reversed for low identifiers, who were more likely to endorse a national apology to Aboriginal Australians when they perceived Aboriginal Australians as rejecting. The role of perceived rejection in predicting prejudice and avoidance, and the moderating role of Asian Australian identification, are both discussed. Copyright © 2009 John Wiley & Sons, Ltd.
Magnetic forces and moving body induced voltages: applications to velocity sensing and DC–AC conversion
Authors: Faria J. A. Brandão
Published: May 2009

This research and tutorial paper illustrates two interlinked phenomena of the greatest importance for power and energy systems engineers, i.e., magnetic forces and moving body induced voltages. A two‐solenoid system with driving and sensing parts is analyzed taking into account that a moving ferromagnetic core can freely move along the system axial coordinate. At first‐order approximation the frequency of the oscillating core movement is shown to be linearly controllable by the direct‐current intensity injected in the driving solenoid. On the other hand the induced voltage on the sensing solenoid is shown to be a sinusoidal voltage with a frequency twice the one of the moving core. Copyright © 2009 John Wiley & Sons, Ltd.
Evolutionary trace of human odorant receptors of chromosome 17
Authors: Knape Kirsten , Beyer Anton , Stary Anna , Buchbauer Gerhard , Wolschann Peter
Published: May 2009

Studies on the odorant receptor cluster located on human chromosome 17, which contains 18 odorant receptor genes, are presented. After an extended search for orthologues of those odorant receptor genes in chimpanzee, rat and mouse genomes, comparisons subject to genomic location, similarities and function were made. Different ways of evolutionary propagation can be observed. This leads to conversion into pseudogenes, but also duplication of some genes occurs. Copyright © 2009 John Wiley & Sons, Ltd.
A novel method for haplotype clustering and visualization
Authors: Teo Yik Y. , Small Kerrin S.
Published: May 2009

In population genetics, it is common to represent the haplotype diversity at a genomic region between multiple populations using well‐constructed visual representations. This typically requires the chromosomes from these populations to be grouped according to some definition of haplotypic similarity. Here, we introduce a novel algorithm for clustering haplotypes with the specific aim of addressing haplotype diversity within or between populations. The algorithm allows for missing data in the haplotypes and appropriately downweighs single nucleotide polymorphisms with higher extent of missingness. By identifying the canonical haplotypes in a genomic region, defined as the haplotype forms, which most chromosomes are similar to, the algorithm maps each chromosome to either a unique canonical haplotype or as a mosaic of the identified canonical haplotypes. This mapping can subsequently be utilized for producing graphical visualizations of the haplotype clustering for understanding the extent of haplotype diversity in the region. The clustering application has been implemented in R for distribution as haplosim, and we also provide a visualization script hapvisual for graphical display of the clustering results. The outcome of such analysis can be informative in understanding the extent of haplotype diversity between populations, in addressing the reproducibility of established association signals across multiple populations, and also in the investigation of positive selection in the human genome. Genet. Epidemiol. 34:34–41, 2010. © 2009 Wiley‐Liss, Inc.
Facial expressions of pain modulate observer's long‐latency responses in superior temporal sulcus
Authors: Kujala Miiamaaria V. , Tanskanen Topi , Parkkonen Lauri , Hari Riitta
Published: May 2009

The strength of brain responses to others' pain has been shown to depend on the intensity of the observed pain. To investigate the temporal profile of such modulation, we recorded neuromagnetic brain responses of healthy subjects to facial expressions of pain. The subjects observed grayscale photos of the faces of genuine chronic pain patients when the patients were suffering from their ordinary pain (Chronic) and when the patients' pain was transiently intensified (Provoked). The cortical activation sequence during observation of the facial expressions of pain advanced from occipital to temporo‐occipital areas, and it differed between Provoked and Chronic pain expressions in the right middle superior temporal sulcus (STS) at 300–500 ms: the responses were about a third stronger for Provoked than Chronic pain faces. Furthermore, the responses to Provoked pain faces were about 40% stronger in the right than the left STS, and they decreased from the first to the second measurement session by one‐fourth, whereas no similar decrease in responses was found for Chronic pain faces. Thus, the STS responses to the pain expressions were modulated by the intensity of the observed pain and by stimulus repetition; the location and latency of the responses suggest close similarities between processing of pain and other affective facial expressions. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.
Functional integration within the human pain system as revealed by Granger causality
Authors: Ploner Markus , Schoffelen Jan‐Mathijs , Schnitzler Alfons , Gross Joachim
Published: May 2009

Pain is a complex experience subserved by an extended network of brain areas. However, the functional integration among these brain areas, i.e., how they interact and communicate to generate a coherent pain percept and an adequate behavioral response is largely unknown. Here, we used magnetoencephalography to investigate functional integration among pain‐related cortical activations in terms of Granger causality and compared it with tactile‐related activations. The results show causal influences of primary somatosensory cortex on secondary somatosensory cortex for tactile‐related but not for pain‐related activations, which supports the proposition of a partially parallel organization of pain processing in the human brain. Furthermore, during a simple reaction time task, the strength of causal influences between somatosensory areas but not the latencies between activations correlated significantly with the speed of reaction times. These findings show how the analysis of functional integration complements traditional analyses of electrophysiological data and provides novel and behaviorally relevant information about the organization of the human pain system. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.
Dysfunctional very-low-density lipoprotein synthesis and release is a key factor in nonalcoholic steatohepatitis pathogenesis # †
Authors: Fujita Koji , Nozaki Yuichi , Wada Koichiro , Yoneda Masato , Fujimoto Yoko , Fujitake Mihoyo , Endo Hiroki , Takahashi Hirokazu , Inamori Masahiko , Kobayashi Noritoshi , Kirikoshi Hiroyuki , Kubota Kensuke , Saito Satoru , Nakajima Atsushi
Published: May 2009

The specific mechanisms of nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH) pathogenesis remain unknown. In the present study we investigated the differences between NAFL and NASH in terms of liver lipid metabolites and serum lipoprotein. In all, 104 Japanese subjects (50 men and 54 postmenopausal women) with histologically verified NAFL disease (NAFLD) (51 with NAFL, 53 with NASH) were evaluated; all diagnoses were based on liver biopsy findings and the proposed diagnostic criteria. To investigate the differences between NAFL and NASH in humans, we carefully examined (1) lipid inflow in the liver, (2) lipid outflow from the liver, (3) very-low-density lipoprotein (VLDL) synthesis in the liver, (4) triglyceride (TG) metabolites in the liver, and (5) lipid changes and oxidative DNA damage. Most of the hepatic lipid metabolite profiles were similar in the NAFL and NASH groups. However, VLDL synthesis and lipid outflow from the liver were impaired, and surplus TGs might have been produced as a result of lipid oxidation and oxidative DNA damage in the NASH group. Conclusion: A growing body of literature suggests that a deterioration in fatty acid oxidation and VLDL secretion from the liver, caused by the impediment of VLDL synthesis, might induce serious lipid oxidation and DNA oxidative damage, impacting the degree of liver injury and thereby contributing to the progression of NASH. Therefore, dysfunctional VLDL synthesis and release may be a key factor in progression to NASH. (Hepatology 2009.)
Expression of Organic Cation Transporters OCT1 (SLC22A1) and OCT3 (SLC22A3) Is Affected by Genetic Factors and Cholestasis in Human Liver†
Authors: Nies Anne T. , Koepsell Hermann , Winter Stefan , Burk Oliver , Klein Kathrin , Kerb Reinhold , Zanger Ulrich M. , Keppler Dietrich , Schwab Matthias , Schaeffeler Elke
Published: May 2009

An important function of hepatocytes is the biotransformation and elimination of various drugs, many of which are organic cations and are taken up by organic cation transporters (OCTs) of the solute carrier family 22 (SLC22). Because interindividual variability of OCT expression may affect response to cationic drugs such as metformin, we systematically investigated genetic and nongenetic factors of OCT1/SLC22A1 and OCT3/SLC22A3 expression in human liver. OCT1 and OCT3 expression (messenger RNA [mRNA], protein) was analyzed in liver tissue samples from 150 Caucasian subjects. Hepatic OCTs were localized by way of immunofluorescence microscopy. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and genome-wide single-nucleotide polymorphism microarray technology served to genotype 92 variants in theSLC22A1-A3/OCT1-3gene cluster. Transport of metformin by recombinant human OCT1 and OCT3 was compared using transfected cells. OCT1 mRNA and protein expression varied 113- and 83-fold, respectively; OCT3 mRNA expression varied 27-fold. OCT1 transcript levels were on average 15-fold higher compared with OCT3. We localized the OCT3 protein to the basolateral hepatocyte membrane and identified metformin as an OCT3 substrate. OCT1 and OCT3 expression are independent of age and sex but were significantly reduced in liver donors diagnosed as cholestatic (P≤ 0.01). Several haplotypes for OCT1 and OCT3 were identified. Multivariate analysis adjusted for multiple testing showed that only the OCT1-Arg61Cys variant (rs12208357) strongly correlated with decreased OCT1 protein expression (P< 0.0001), and four variants inOCT3(rs2292334, rs2048327, rs1810126, rs3088442) were associated with reduced OCT3 mRNA levels (P= 0.03).

Conclusion:

We identified cholestasis and genetic variants as critical determinants for considerable interindividual variability of hepatic OCT1 and OCT3 expression. This indicates consequences for hepatic elimination of and response to OCT substrates such as metformin. (Hepatology 2009.)
Angiotensin-converting-enzyme 2 inhibits liver fibrosis in mice #
Authors: Österreicher Christoph H. , Taura Kojiro , De Minicis Samuele , Seki Ekihiro , Penz-Österreicher Melitta , Kodama Yuzo , Kluwe Johannes , Schuster Manfred , Oudit Gavin Y. , Penninger Josef M. , Brenner David A.
Published: May 2009

The renin-angiotensin system (RAS) plays a major role in liver fibrosis. Recently, a homolog of angiotensin-converting-enzyme 1 (ACE1), termed ACE2, has been identified that appears to be a negative regulator of the RAS by degrading Ang II to Ang1-7. The aim of this study was to characterize the long-term effects of gene deletion of ACE2 in the liver, to define the role of ACE2 in acute and chronic liver disease, and to characterize the role of Ang1-7 in hepatic stellate cell (HSC) activation. Ace2 knockout (KO) mice and wild-type (wt) littermates underwent different models of acute and chronic liver injury. Liver pathology was analyzed by histology, immunohistochemistry, alpha smooth muscle actin (α-SMA) immunoblotting, and quantitative polymerase chain reaction (qPCR). Murine HSCs were isolated by collagenase-pronase-perfusion, and density gradient centrifugation. One-year-old ace2 KO mice spontaneously developed an inflammatory cell infiltration and mild hepatic fibrosis that was prevented by treatment with irbesartan. Ace2 KO mice showed increased liver fibrosis following bile duct ligation for 21 days or chronic carbon tetrachloride (CCl4) treatment. In contrast, ace2 KO mice subjected to acute liver injury models did not differ from wt littermates. Treatment with recombinant ACE2 attenuated experimental fibrosis in the course of cholestatic and toxic liver injury. HSCs express the Ang1-7 receptor Mas and Ang1-7 inhibited Ang II-induced phosphorylation of extracellular signal-regulated kinase (ERK)-1/2 in cultured HSCs. Conclusion: ACE2 is a key negative regulator of the RAS and functions to limit fibrosis through the degradation of Ang II and the formation of Ang1-7. Whereas loss of ACE2 activity worsens liver fibrosis in chronic liver injury models, administration of recombinant ACE2 shows therapeutic potential. (Hepatology 2009.)
Fornix transection selectively impairs fast learning of conditional visuospatial discriminations
Authors: Kwok Sze Chai , Buckley Mark J.
Published: May 2009

As the fornix has previously been implicated in the rapid learning of associations, we hypothesized that fornix transection in macaques would selectively impair the acquisition of rapidly learned conditional visuospatial discrimination problems. Macaque monkeys learned, postoperatively, three sets of concurrent problems of increasing sizes containing 8, 32, and 64 problems, respectively. Each problem consisted of four identical visual stimuli and animals had to learn which stimulus position was rewarded. The lesioned animals made significantly more errors‐to‐criterion on the smallest set of problems, consistent with the idea that the most rapidly acquired sets would be more vulnerable to fornical damage. Moreover, during the early stages of acquisition across all three sets, fornix transection selectively impeded monkeys' abilities to eliminate nonperseverative errors in correction trials, consistent with an inability to monitor or correct erroneous spatial responses made further back in time than the last trial. Both one‐trial learning and an errorless learning (facilitation of performance) were observed in control and fornix lesioned animals but neither were fornix‐dependent and overcoming the deleterious effect upon subsequent learning of having made prior errors was also unaffected by fornix transection. The data indicate that the fornix is not important for all forms of new learning; rather it is selectively concerned with the relatively rapid acquisition of spatial and temporal relationships between stimuli and responses. © 2009 Wiley‐Liss, Inc.

This article was published online on 27 May 2009. An error was subsequently identified. This notice is included in the online and print versions to indicate that both have been corrected 11 June 2009.