bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment of chronic anorexia nervosa: a 4‐year follow‐up of adult patients treated in an acute inpatient setting
Authors: Long Clive G. , Fitzgerald Kirsty‐Anne , Hollin Clive R.
Published: February 2011

Despite evidence from a number of long‐term follow‐up studies of anorexia nervosa that nearly 50% of patients eventually make a full recovery, controlled trials of psychotherapy for anorexia nervosa are lacking. Those with severe and enduring problems represent a considerable therapeutic challenge. Thirty‐four consecutive adult referrals to the inpatient treatment unit who fulfilled Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnostic criteria for anorexia nervosa were examined pre‐admission, post‐discharge and 4 years after admission. Characteristics of remitted and non‐remitted patients were examined. Secondary analyses considered the differences between patients with anorexia nervosa, restricting type and anorexia nervosa binging/purging type. The findings highlight a number of differences between patients with anorexia nervosa (restricting type) versus anorexia nervosa (binging/purging type) as well as remitted versus non‐remitted patients. The use of a comprehensive battery of assessments found that resolution of eating disorder symptomatology was paralleled by improvements in emotional and psychological distress and improvement in body image perception and coping skills. Better results were obtained for those who had continuity of care on an outpatient basis. This pattern is particularly significant given the more ‘chronic’ nature of the sample that were older, with a higher incidence of binge‐eating and purging than previous samples. Results provide some encouragement for the treatment of those adults with anorexia nervosa who typically have less favourable outcomes. Copyright © 2011 John Wiley & Sons, Ltd.

Key Practitioner Message:

• Patients with chronic anorexia nervosa provide a significant therapeutic challenge. An eclectic, multidisciplinary treatment approach that focuses on treatment readiness and its therapeutic alliance is advocated along with continuity of care between inpatients and outpatients stages.
Growth and forms of spherulitic crystal pattern in a Belousov‐Zhabotinski type reaction system
Authors: Yadav N. , Srivastava P. K.
Published: February 2011

The growth of spherulitic like crystal patterns in a dual substrate Belousov–Zhabotinski (BZ) reaction system has been studied. The solution phase reaction has been found to show concentric ring like wave pattern. A colloidal phase consisting of numerous fine solid particles have also been observed during reaction process, which initially forms the solid phase nucleation centers of dendritic character, and subsequently grow into spherulitic like crystal patterns. The reaction mechanism has been proposed, which illustrate possible reaction products formed during solution phase reaction that are inevitably involved in the formation of the dendritic nucleation centers. The spherulitic crystal pattern has been found to show transition in morphology by substituted organic substrate.The transition behaviour of crystal pattern has also been described and discussed. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Seed loading effects on the mean crystal size of acetylsalicylic acid in a continuous‐flow crystallization device
Authors: Eder R. J. P. , Schmitt E. K. , Grill J. , Radl S. , Gruber‐Woelfler H. , Khinast J. G.
Published: February 2011

This study investigates the effects of seed loading on the mean crystal size of the model substance, acetylsalicylic acid, crystallized from ethanol in a continuously seeded tubular crystallizer. A hot, highly concentrated ethanolic acetylsalicylic acid solution was mixed with an acetylsalicylic acid‐ethanol seed suspension. Subsequent cooling of the slurry in the tubing promoted supersaturation and hence crystal growth. The tubular shape of the 15 m‐long crystallizer with an inner diameter of 2 mm enabled narrow residence time distributions of the crystals in the pipe and excellent temperature control in the radial direction and along the tubing. Crystals entering the crystallizer had both identical growth conditions in each section and about the same time for crystal growth. Narrow crystal size distributions were achieved with decreasing differences in the volume‐mean‐diameter sizes of the seed and product crystals as seed loadings increased. Decreasing the seed size had a similar effect as increasing the seed loading, since in that case the same amount of seed mass resulted in more individual seed particles. Altering the arrangement of the coiled crystallizer with respect to spatial directions (horizontal, vertical) did not lead to a significantly different outcome. All experiments produced considerably larger product crystals in comparison to the seeds despite relatively short crystallization times of less than 3 min. Moreover, product mass gains of a few hundred percent at a g/min‐scale were achieved. Similarities in product crystal samples taken at different times at the outlet of the crystallizer showed that steady‐state conditions were rapidly reached in the continuous flow crystallization device. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Hydrothermal synthesis of highly symmetric 26‐facet Cu2O polyhedra
Authors: Wang Wei , Liao Zhigang , Wang Yi , Wu Xiang , Qu Fengyu , Zhang Xu
Published: February 2011

Highly symmetric 26‐facet polyhedral microcrystals of cuprous oxide (Cu2O) are successfully synthesized through a facile low temperature hydrothermal reaction. These polyhedra are constructed by well‐developed {100}, {110} and {111} crystallographic faces. The obtained microstructures were characterized by X‐ray diffraction (XRD), field emission scanning electron microscopy (FESEM), and Ultraviolet‐Visible (UV‐Vis) absorption spectrum. Cetyltrimethyl ammonium bromide (CTAB) and ethylenediaminetetraacetic acid disodium (EDTA‐2Na) have been confirmed to be necessary additives to the development of these perfect polyhedra. The growth process of the 26‐facet Cu2O polyhedra is depicted on the grounds of the time‐dependent experiments. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Influence of transverse magnetic field on thermocapillary flow in liquid bridge
Authors: Li Xiaohong , Zeng Zhong , Yao Liping , Li Liang , Chen Chaobo , Zhang Yongxiang , Chen Jingqiu
Published: February 2011

For exploring the optimizing convection control technique by external magnetic field in floating zone crystal growth of semiconductor under microgravity, thermocapillary flow in a floating half‐zone model is simulated numerically, and the influences of both the transversal uniform magnetic field and the magnetic field generated by transversal four coils on thermocapillary flow are investigated. The results indicate that the transversal uniform magnetic field is likely to break the axisymmetrical structure of thermocapillary flow, which is unfavorable to the growth of high‐quality crystal; under the magnetic field generated by transversal four coils, both the mean and the maximum velocities increase with the increment of the distance between coils or the decrement of coil radius; and the convection tends to be more axisymmetrical with increasing coil radius. Compared to the transversal uniform magnetic field, the magnetic field generated by transversal four coils of appropriate radius and relative distance may not only suppress convection, but also enhance the axisymmetry of convection at the same time, and finally, the better convection control can be achieved. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Floating zone growth and characterization of ruby single crystals
Authors: Fan Xiujun , Wang Yue , Xu Hong , Jiang Yijian
Published: February 2011

Large, high optical quality single crystals of ruby have been grown successfully by the floating zone method under air atmosphere. The size of the grown crystal is typically 60‐70 mm in length and 7‐8 mm in diameter. The obtained crystals were red and did not have any macroscopic defects such as cracks and inclusions. Grown crystals were characterized by powder X‐ray diffraction (XRD) methods, polarized optical microscopy, scanning electron microscopy (SEM). The absorption and fluorescence spectra were measured at room temperature and the dielectric constant measurements of ruby crystals were also presented. Defects occurring in single crystals of ruby during crystal growth by floating zone method are described, and their correlation with the growth parameters is discussed. The origin and control of these defects in grown crystals were studied and the optimum method was proposed. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Determining the stability margin in linear interval parameter electric circuits via a DAE model
Authors: Kolev Lubomir
Published: February 2011

This paper addresses the problem of determining the stability margin Ms in linear time‐invariant electric circuits whose parameters R, L, C, M and controlled source coefficients α are allowed to take on fixed but unknown values within corresponding preset intervals. A method for solving the above robust stability problem is suggested. Unlike previous results resorting to the state–space formulation, the new method is based on an appropriate description of the circuit considered using a specific model in semi‐state form. The set of differential algebraic equations (DAEs) thus obtained contain the circuit parameters in a linear manner. The latter property permits Ms to be determined in an efficient way using the right endpoint of the range related to the real part of the first (closest to the imaginary axis) eigenvalue of a corresponding interval generalized eigenvalue problem. The new method is shown to have polynomial numerical complexity with respect to the size of the generalized eigenvalue problem. Two numerical examples illustrating the new DAE approach are provided. Copyright © 2011 John Wiley & Sons, Ltd.
Interoperability of time series cytometric data: A cross platform approach for modeling tumor heterogeneity
Authors: Khan Imtiaz A. , Lupi Monica , Campbell Lee , Chappell Sally C. , Brown M. Rowan , Wiltshire Marie , Smith Paul J. , Ubezio Paolo , Errington Rachel J.
Published: February 2011

The cell cycle, with its highly conserved features, is a fundamental driver for the temporal control of cell proliferation—while abnormal control and modulation of the cell cycle are characteristic of tumor cells. The principle aim in cancer biology is to seek anunderstanding of the origin and nature of innate and acquired heterogeneity at the cellular level, driven principally by temporal and functional asynchrony. A major bottleneck when mathematically modeling these biological systems is the lack of interlinked structured experimental data. This often results in the in silico models failing to translate the specific hypothesis into parameterized terms that enable robust validation and hence would produce suitable prediction tools rather than just simulation tools. The focus has been on linking data originating from different cytometric platforms and cell‐based event analysis to inform and constrain the input parameters of a compartmental cell cycle model, hence partly measuring and deconvolving cell cycle heterogeneity within a tumor population. Our work has addressed the concept that the interoperability of cytometric data, derived from different cytometry platforms, can complement as well as enhance cellular parameters space, thus providing a more broader and in‐depth view of the cellular systems. The initial aim was to enable the cell cycle model to deliver an improved integrated simulation of the well‐defined and constrained biological system. From a modeling perspective, such a cross platform approach has provided a paradigm shift from conventional cross‐validation approaches, and from a bioinformatics perspective, novel computational methodology has been introduced for integrating and mapping continuous data with cross‐sectional data. This establishes the foundation for developing predictive models and in silico tracking and prediction of tumor progression. © 2011 International Society for Advancement of Cytometry.
A novel IEEE 802.11‐based MAC protocol supporting cooperative communications
Authors: Liu Wei , Jin Huan , Wang Xinbing , Guizani Mohsen
Published: February 2011

Cooperative diversity is a transmission technique, where multiple terminals form a virtual antenna array that realizes spatial diversity gain in a distributed fashion. The concept of cooperation has already been introduced to MAC layer to design MAC protocol. But it does not take advantage of physical layer's cooperation. In this paper, we present a novel MAC protocol based on IEEE 802.11, called C‐MAC, which is able to support the basic building block of cooperative system. In other words, in C‐MAC, a source would invite a relay node into data transmission if there exits an available one. During data transmission, the source sends the signal to destination in the first time slot. The relay node will retransmit the overheard information to the destination in the second time slot. The destination combines two signals from the source and the helper to create the spatial diversity and robustness against channel fading. The C‐MAC is backward compatible to the legacy IEEE 802.11 system. The performance of C‐MAC mainly depends on physical layer's performance as it just provides the support for cooperation at the MAC layer. If the physical layer works well, C‐MAC would outperform IEEE 802.11 when considering packet error rate (PER). We also perform extensive simulation using ns‐2 with assumptive physical parameters. The results show that C‐MAC would outperform 802.11 if PER is over some threshold, e.g. when PER is 0.4, C‐MAC can achieve up to 11.5% higher throughput than IEEE 802.11. Copyright © 2011 John Wiley & Sons, Ltd.
The eating disorders examination in adolescent males with anorexia nervosa: How does it compare to adolescent females?
Authors: Darcy Alison M. , Doyle Angela Celio , Lock James , Peebles Rebecka , Doyle Peter , Le Grange Daniel
Published: February 2011

Objective:

The study aimed to explore the Eating Disorder Examination (EDE) for adolescent males with eating disorders (EDs) compared with adolescent females with EDs.

Method:

Data were collected from 48 males and matched on percent median body weight (MBW) and age to 48 females at two sites.

Results:

Adolescent males with anorexia nervosa‐type presentation scored significantly lower than matched females on Shape Concern, Weight Concern, and Global score. They also scored lower on a number of individual items.

Discussion:

The EDE has clinical utility with adolescent males with anorexic‐type presentation although males' scoring ranges are consistently lower than those from adolescent females with similar clinical presentations. Males scored significantly lower on a number of items representing core symptoms such as desire to lose weight. More research is needed to gain a better understanding of the experience of adolescent males with EDs, particularly in relation to the nature of shape concern. © 2011 by Wiley Periodicals, Inc. (Int J Eat Disord 2012)
Secondary CD8+ T‐cell responses are controlled by systemic inflammation
Authors: Wirth Thomas C. , Martin Matthew D. , Starbeck‐Miller Gabriel , Harty John T. , Badovinac Vladimir P.
Published: February 2011

Repeated infections and experimental prime‐boost regimens frequently result in the generation of secondary (2°) CD8+ T‐cell responses. In contrast to primary (1°) CD8+ T cells, the parameters that influence the abundance and phenotype of 2° effector and memory CD8+ T‐cell populations are largely unknown. Here, we analyze the impact of different booster infections, Ag curtailment, and systemic inflammation on the quality and quantity of secondary CD8+ T‐cell responses. We show that similar to 1° CD8+ T‐cell responses, the phenotype of 2° effector and memory CD8+ T‐cell populations is critically dependent on the nature of the infectious pathogen and the inflammatory milieu early after infection. In addition, systemic inflammation increases the number of 2° effector and memory CD8+ T cells after booster infections and immunizations. Therefore, our data reveal new means to boost the number of 2° effector and memory CD8+ T cells in prime‐boost regimens and show a surprisingly high degree of plasticity in 2° memory CD8+ T‐cell phenotype that is controlled by systemic inflammation.
Mechanistic Insights into the Reaction of Enantiomerically Pure Lithiosilanes and Electrophiles: Understanding the Differences between Aryl and Alkyl Halides
Authors: Däschlein Christian , Bauer Simeon O. , Strohmann Carsten
Published: February 2011

The reactivity of enantiomerically pure lithiosilanes against aliphatic and aromatic halo electrophiles has been investigated with the focus on product composition and enantiomeric ratios as a basis for a better understanding of ongoing mechanisms. Both parameters are strongly influenced by both the organic group and the corresponding halide of the used electrophile. Thus, high stereoselectivities and yields are only obtained if one distinct reaction mechanism dominates. In the case of aliphatic electrophiles, experimental and quantum chemical studies support the preference of an SN2 mechanism for chlorides resulting in retention of configuration on silicon, whereas bromides tend to react under inversion through a halide–lithium exchange (ate complex). For aromatic electrophiles these relationships change: chlorides and bromides both favor the formation of an ate complex over nucleophilic aromatic substitution, leading to inversion of configuration on silicon.
Coordination of a Hemilabile N,N,S Donor Ligand in the Redox System [CuL2]+/2+, L = 2‐Pyridyl‐N‐(2′‐alkylthio­phenyl)methyleneimine
Authors: Schnödt Johannes , Manzur Jorge , García Ana‐Maria , Hartenbach Ingo , Su Cheng‐Yong , Fiedler Jan , Kaim Wolfgang
Published: February 2011

The new copper(I) complexes [Cu(L1)2](BF4), L1 = 2‐pyridyl‐N‐(2′‐methylthiophenyl)methyleneimine, and [Cu(L2)2](ClO4), L2 = 2‐pyridyl‐N‐(2′‐benzylthiophenyl)methyleneimine, have been prepared and structurally characterized. In contrast to the known [Cu(L1)2](ClO4)2, which exhibits partial thioether S binding to effect five‐coordinate Cu2+, the copper(I) compounds reported here contain four‐coordinate metal ions with exclusively N‐donor binding. Cyclic voltammetry reveals a fully reversible oxidation of the CuI species, which suggests a small barrier for reorganization. The reduction at negative potentials is irreversible for compounds [Cu(L)2](X) and for the structurally characterized new compound [Cu(L1)(PPh3)2](ClO4). UV/Vis spectroelectrochemistry shows the typical low‐energy absorption bands of copper(I) (MLCT transition) and copper(II) (ligand‐field transition) in the visible region; the CuII form develops an intense band at 350 nm attributed to a S‐to‐Cu ligand‐to‐metal charge transfer (LMCT).
Asymmetric Organocatalytic Aza‐Friedel–Crafts Reaction of Naphthols with N‐Sulfonyl Imines
Authors: Chauhan Pankaj , Chimni Swapandeep Singh
Published: February 2011

The first organocatalytic asymmetric aza‐Friedel–Crafts reaction of naphthols with N‐sulfonyl imines has been developed. The cupreine‐derived bifunctional organocatalyst BzCPN efficiently catalyzes the formation of aza‐Friedel–Crafts products in good to excellent yields (up to 99 %) with high enantioselectivities (up to 99.5:0.5 er) under mild reaction conditions, with a low catalyst loading (2–5 mol‐%), and in an aerobic environment.
Mechanically Interlocked Porphyrin Gears Propagating Two Different Rotational Frequencies
Authors: Ogi Soichiro , Ikeda Tomohiro , Wakabayashi Rie , Shinkai Seiji , Takeuchi Masayuki
Published: February 2011

We report a new supramolecular rotor (1), in which a lanthanum(III) bis(porphyrinate)s double‐decker (LaDD) bears two porphyrinatorhodium(III)‐based rotors whose planes aresituated orthogonally to one another. In [D2]dichloromethane, 1H NMR spectral results indicated that rotational information was transmitted from the LaDD rotor to two porphyrinatorhodium(III)‐based rotors through mechanical interaction of the teeth of the rotors. Mechanical interaction was achieved among the multiple rotors in 1 even after switching the rotational activity of the LaDD rotor by using [D5]pyridine. The spatial arrangement of the two porphyrinatorhodium(III)‐based rotors is a critical factor in maintaining mechanical interaction between multiple molecular rotors when changing the dynamic properties of one rotor.
Components of the Net Current in Differential Pulse Polarography. Part 2. Kinetics and Adsorption
Authors: Zelić Marina , Lovrić Milivoj
Published: February 2011

Components of the net response in differential pulse polarography were studied theoretically, assuming gradually changing electrode rate constant or strength of the reactant adsorption. The difference between the maximum potential of the peak component and the half‐wave potential of the wave component appear as an important parameter. From its value, the electrode rate constant can be calculated even when the standard potential is not known. In a reversible process, effects of the reactant adsorption on the mentioned separation are less pronounced. The results were compared with experimentally obtained effects. For deeper insight into the applicability of this approach, additional experimentally obtained polarograms (that reflect different potential/timing parameters or changing character of the electrode process) should be studied in terms of their components.
Impact of the Gold Support on the Electrocatalytic Oxidation of Sugars at Enzyme‐Modified Electrodes
Authors: Vidaković‐Koch Tanja , Ivanov Ivan , Falk Magnus , Shleev Sergey , Ruzgas Tautgirdas , Sundmacher Kai
Published: February 2011

The influence of gold support on the bioelectrocatalytic activity of glucose oxidase and cellobiose dehydrogenase immobilized on self‐assembled monolayer‐modified high surface area gold electrodes such as rough gold and gold nanoparticles has been studied. The two types of enzyme‐modified electrodes showed very high activity towards sugar oxidation. However, it has been shown that the largest part of this electrocatalytic activity comes from the underlying gold surface. These findings are of special importance for bioelectrochemical studies of enzymatic electrodes, where the immobilization support might show electrocatalytic properties toward the substrates of investigated enzymes.
In vitro cormlet production and growth evaluation under greenhouse conditions in saffron (Crocus sativus L.) – A commercially important crop
Authors: Devi Kiran , Sharma Madhu , Singh Markandey , Singh Ahuja Paramvir
Published: February 2011

The present study describes the effects of season on initial bud sprouting, direct shoot regeneration from the base of the sprouted bud, and cormlet production from multiple shoots, and provides growth evaluation of in vitro produced cormlets under greenhouse conditions. Initial sprouting of buds from corm segments was previously described in medium supplemented with 2,4‐dichlorophenoxyacetic acid (2,4‐D, 9.05 μM) and 6‐benzylaminopurine (BAP, 26.64 μM). Maximum bud sprouting (90%) was observed during November and December. Direct multiple shoot primordia were initiated from the base of these sprouted buds on BAP (26.64 μM). Multiplication of shoots was achieved in BAP (26.64 μM) and α‐naphthalene acetic acid (1.0 and 5.0 μM). Growth retardants (chlorocholine chloride and paclobutrazol) were used for cormlet production from multiple shoots, and paclobutrazol (1.7 μM) evinced maximum cormlet production (86.07%). Growth of these in vitro‐produced cormlets was evaluated under greenhouse conditions, and 91.66% sprouting was observed. An increase in cormlet weight (66.88%) was also observed under in vivo conditions.
New staging system and a registry for perihilar cholangiocarcinoma
Authors: DeOliveira Michelle L. , Schulick Richard D. , Nimura Yuji , Rosen Charles , Gores Gregory , Neuhaus Peter , Clavien Pierre-Alain
Published: February 2011

Perihilar cholangiocarcinoma is one of the most challenging diseases with poor overall survival. The major problem for anyone trying to convincingly compare studies among centers or over time is the lack of a reliable staging system. The most commonly used system is the Bismuth-Corlette classification of bile duct involvement, which, however, does not include crucial information such as vascular encasement and distant metastases. Other systems are rarely used because they do not provide several key pieces of information guiding therapy. Therefore, we have designed a new system reporting the size of the tumor, the extent of the disease in the biliary system, the involvement of the hepatic artery and portal vein, the involvement of lymph nodes, distant metastases, and the volume of the putative remnant liver after resection. The aim of this system is the standardization of the reporting of perihilar cholangiocarcinoma so that relevant information regarding resectability, indications for liver transplantation, and prognosis can be provided. With this tool, we have created a new registry enabling every center to prospectively enter data on their patients with hilar cholangiocarcinoma (). The availability of such standardized and multicenter data will enable us to identify the critical criteria guiding therapy. (HEPATOLOGY 2011;)
Hepatic encephalopathy: A central neuroinflammatory disorder?
Authors: Butterworth Roger F.
Published: February 2011

Encephalopathy and brain edema are serious central nervous system complications of liver failure. Recent studies using molecular probes and antibodies to cell-specific marker proteins have demonstrated the activation of microglial cells in the brain during liver failure and confirmed a central neuroinflammatory response. In animal models of ischemic or toxic liver injury, microglial activation and concomitantly increased expression of genes coding for proinflammatory cytokines in the brain occur early in the progression of encephalopathy and brain edema. Moreover, the prevention of these complications with mild hypothermia or

N

-acetylcysteine (two treatments known to manifest both peripheral and central cytoprotective properties) averts central neuroinflammation due to liver failure. Recent studies using anti-inflammatory agents such as ibuprofen and indomethacin have shown promise for the treatment of mild encephalopathy in patients with cirrhosis, whereas treatment with minocycline, a potent inhibitor of microglial activation, attenuates the encephalopathy grade and prevents brain edema in experimental acute liver failure. The precise nature of the signaling mechanisms between the failing liver and central neuroinflammation has yet to be fully elucidated; mechanisms involving blood-brain cytokine transfer and receptor-mediated cytokine signal transduction as well as a role for liver-related toxic metabolites such as ammonia have been proposed. The prevention of central proinflammatory processes will undoubtedly herald a new chapter in the development of agents for the prevention and treatment of the central nervous system complications of liver failure. (HEPATOLOGY 2011;)
Drug-induced cholestasis
Authors: Padda Manmeet S. , Sanchez Mayra , Akhtar Abbasi J. , Boyer James L.
Published: February 2011

Recent progress in understanding the molecular mechanisms of bile formation and cholestasis have led to new insights into the pathogenesis of drug-induced cholestasis. This review summarizes their variable clinical presentations, examines the role of transport proteins in hepatic drug clearance and toxicity, and addresses the increasing importance of genetic determinants, as well as practical aspects of diagnosis and management. (HEPATOLOGY 2011;)
Hepatocyte-targeted expression by integrase-defective lentiviral vectors induces antigen-specific tolerance in mice with low genotoxic risk
Authors: Mátrai Janka , Cantore Alessio , Bartholomae Cynthia C. , Annoni Andrea , Wang Wei , Acosta-Sanchez Abel , Samara-Kuko Ermira , De Waele Liesbeth , Ma Ling , Genovese Pietro , Damo Martina , Arens Anne , Goudy Kevin , Nichols Timothy C. , von Kalle Christof , L. Chuah Marinee K. , Roncarolo Maria Grazia , Schmidt Manfred , VandenDriessche Thierry , Naldini Luigi
Published: February 2011

Lentiviral vectors are attractive tools for liver-directed gene therapy because of their capacity for stable gene expression and the lack of preexisting immunity in most human subjects. However, the use of integrating vectors may raise some concerns about the potential risk of insertional mutagenesis. Here we investigated liver gene transfer by integrase-defective lentiviral vectors (IDLVs) containing an inactivating mutation in the integrase (D64V). Hepatocyte-targeted expression using IDLVs resulted in the sustained and robust induction of immune tolerance to both intracellular and secreted proteins, despite the reduced transgene expression levels in comparison with their integrase-competent vector counterparts. IDLV-mediated and hepatocyte-targeted coagulation factor IX (FIX) expression prevented the induction of neutralizing antibodies to FIX even after antigen rechallenge in hemophilia B mice and accounted for relatively prolonged therapeutic FIX expression levels. Upon the delivery of intracellular model antigens, hepatocyte-targeted IDLVs induced transgene-specific regulatory T cells that contributed to the observed immune tolerance. Deep sequencing of IDLV-transduced livers showed only rare genomic integrations that had no preference for gene coding regions and occurred mostly by a mechanism inconsistent with residual integrase activity.

Conclusion:

IDLVs provide an attractive platform for the tolerogenic expression of intracellular or secreted proteins in the liver with a substantially reduced risk of insertional mutagenesis. (Hepatology 2011;)
Loss of phosphatase and tensin homolog enhances cell invasion and migration through aKT/Sp-1 transcription factor/matrix metalloproteinase 2 activation in hepatocellular carcinoma and has clinicopathologic significance
Authors: Sze Karen Man-Fong , Wong Kris Lai-Ting , Chu Glanice Kin-Yan , Lee Joyce Man-Fong , Yau Tai-On , Oi-Lin Ng Irene
Published: February 2011

Phosphatase and tensin homolog (PTEN) is frequently inactivated in cancers and is associated with advanced stages of cancers or metastasis. However, the molecular mechanism of PTEN in hepatocellular carcinoma (HCC) metastasis is unclear. In this study, we found frequent (47.5%, n = 40) protein underexpression of PTEN in human HCCs compared with their corresponding nontumorous livers. Significantly, PTEN underexpression was associated with larger tumor size (

P

= 0.021), tumor microsatellite formation (

P

= 0.027), and shorter overall survival of patients (

P

= 0.035). Using different cell models, we observed that PTEN-knockdown HCC cells and PTEN-knockout mouse embryonic fibroblasts (MEFs) had enhanced cell migratory and invasive abilities. In addition to activation of AKT, there was up-regulation of the Sp1 transcription factor (SP1) and matrix metalloproteinase 2 (MMP2), as well as MMP2 activation in PTEN-knockdown HCC cells and PTEN−/− MEFs. With dual luciferase reporter assay, exogenous expression of SP1 in HCC cells led to enhanced MMP2 promoter activity by up to 74%, whereas deletion of the putative SP1 binding site on the MMP2 promoter led to reduced promoter activity by up to 65%. Using chromatin immunoprecipitation assay, we documented increased binding of SP1 to the MMP2 promoter in PTEN-knockdown HCC cells. Overexpression of SP1 and MMP2 was significantly but negatively associated with PTEN underexpression in human HCCs.

Conclusion:

Our results show that PTEN was underexpressed in HCCs, and this underexpression was associated with more aggressive biological behavior and poorer patient survival. We have provided the first evidence that MMP2 up-regulation upon PTEN loss is SP1-dependent. Our findings indicate that PTEN plays a significant role in down-regulating HCC cell invasion via the AKT/SP1/MMP2 pathway. (Hepatology 2011;)
New Patchoulol‐Type Sesquiterpenoids from Pogostemon cablin
Authors: Zhou Lei , Xu Min , Yang Chong‐Ren , Wang Yi‐Fei , Zhang Ying‐Jun
Published: February 2011

Four new patchoulol derivatives, 8α,9α‐dihydroxypatchoulol (1), 3α,8α‐dihydroxypatchoulol (2), 6α‐hydroxypatchoulol (3), and 2β,12‐dihydroxypatchoulol (4), were isolated from the aerial part of Pogostemon cablin (Labiatae), together with nine known compounds, sesquiterpenoids 5–8 and flavonoids 9–13. Their structures were elucidated by detailed spectroscopic analysis, using 1D‐ and 2D‐NMR techniques.
Cycloartane Glycosides from Three Species of Astragalus (Fabaceae)
Authors: Linnek Jens , Mitaine‐Offer Anne‐Claire , Miyamoto Tomofumi , Tanaka Chiaki , Paululat Thomas , Avunduk Sibel , Alankuş‐Çalişkan Özgen , Lacaille‐Dubois Marie‐Aleth
Published: February 2011

Nine cycloartane‐type glycosides were isolated from three species of the genus Astragalus (Fabaceae): From the aerial parts of A. cicer L., two new saponins, cicerosides A and B (1 and 2, resp.), i.e., a tetradesmosidic and tridesmosidic cycloartane‐type glycosides besides one known compound, from the roots of A. sempervirens Lam., one known saponin, and from the roots of A. ptilodes Boiss. var. cariensis Boiss., five known compounds. Their structures were established mainly by 600‐MHz 2D‐NMR techniques (1H,1H‐COSY, TOCSY, NOESY, HSQC, and HMBC) and mass spectroscopy.
Optical Resolution and Structure Determination of New Indolizidine Alkaloids from Elaeocarpus sphaericus
Authors: Zhou Chang‐Xin , Wang Xue‐Yao , Mo Jian‐Xia , Zhang Jian , Gan Li‐She
Published: February 2011

Two new indolizidine alkaloids, (±)‐3‐oxoisoelaeocarpine (1) and (±)‐elaeocarpine N‐oxide (2), along with three known alkaloids, (±)‐isoelaeocarpine (3), (±)‐elaeocarpine (4), and (−)‐isoelaeocarpiline (5), were isolated from an EtOH extract of the branches and leaves of Elaeocarpus sphaericus. The structures of these compounds were determined by spectroscopic and chemical methods. Furthermore, enantiomers of compounds 1 and 3 were separated on a chiral CD‐Ph column, and their absolute configurations were determined by TD‐DFT (=time‐dependent density‐functional theory) quantum‐chemical calculations of their electronic circular dichroism (ECD) spectra.
Comparison of Dinitrogen, Methane, Carbon Monoxide, and Carbon Dioxide Mass‐Transport Dynamics in Carbon and Zeolite Molecular Sieves
Authors: Onyestyák György
Published: February 2011

Equilibrium (based on Henry constants) and kinetic (based on relaxation‐time constants or rather macropore transport diffusivities) selectivities for commercial zeolite and carbon‐molecular‐sieve (CMS) adsorbents were compared. Adsorption isotherms were recorded at −20°. The frequency‐response (FR) sorption‐rate spectra were determined in the range of −78 and 70° at 133 Pa. In particles of a larger size than 1.0 mm, macropore diffusion governed the rate of sorption mass transport in both types of microporous materials. The differences in the intercrystalline diffusivities established the kinetic separation of the gases notwithstanding the essential importance of interactions in the micropores. Zeolites seem to be more advantageous for a dynamic separation of CO2 and CH4 than CMS 4A. With the CO2 and CO pair, the CMS is characterized by short characteristic times which, together with a good separation factor, is a double advantage in a short‐cycle adsorption technology. Upon comminution of the carbon pellets, intercrystalline‐diffusion resistance can be completely removed by using CMS 4A adsorbent particles with a diameter smaller than 1 mm. The carbonization of spruce‐wood cubes resulted in an excellent carbon honeycomb structure, which seems to be ideal from a dynamic point of view for applications in short‐cycle adsorption‐separation technologies. In the development of adsorbents, the use of the FR method can be beneficial.
On the Ligand‐to‐Metal Charge‐Transfer Photochemistry of the Copper(II) Complexes of Quercetin and Rutin
Authors: Torres Simonet , Ferraudi Guillermo , Aguirre Maria Jesus , Isaacs Mauricio , Matsuhiro Betty , Chandía Nancy P. , Mendoza Leonora
Published: February 2011

In contrast to the UV‐photoinduced ligand photoionization of the flavonoid complexes of FeIII, redox reactions initiated in ligand‐to‐metal charge‐transfer excited states were observed on irradiation of the quercetin (1) and rutin (2) complexes of CuII. Solutions of complexes with stoichiometries [CuIIL2] (L=quercetin, rutin) and [CuII2Ln] (n=1, L=quercetin; n=3, L=rutin) were flash‐irradiated at 351 nm. Transient spectra observed in these experiments showed the formation of radical ligands corresponding to the one‐electron oxidation of L and the reduction of CuII to CuI. The radical ligands remained coordinated to the CuI centers, and the substitution reactions replacing them by solvent occurred with lifetimes τ<350 ns. These are lifetimes shorter than the known lifetimes (τ>1 ms) of the quercetin and rutin radical's decay.
An Efficient Photoinduced Deprotection of Aromatic Acetals and Ketals
Authors: Thevenet Damien , Neier Reinhard
Published: February 2011

A novel type of photodeprotection reaction of simple aromatic acetals and ketals is described. The deprotection is highly efficient under optimized conditions. The aromatic ring confers the photoreactivity to the compounds. The efficiency of the process depends on the structure of the acetal moiety. The common minor side reaction, the photooxidation, becomes the major reaction pathway in the cases of cyclic acetals. The use of photon as only reagent makes this procedure especially attractive for acetal deprotection.
In vitro and in vivo evaluation of the effects of duloxetine on P‐gp function
Authors: Ruike Zhao , Junhua Cao , Wenxing Peng
Published: February 2011

Objective

To evaluate the effect of duloxetine (DLX) on the P‐glycoprotein (P‐gp) function in vitro and in vivo.

Method

In vitro experiment was conducted using the Caco‐2 cell, a human colon cancer cell line that naturally expresses the P‐gp and P‐gp function was evaluated by monitoring whether DLX affect the accumulation of Rhd123. In vivo study was conducted by quantitating the effect of orally administered DLX on the bioavailability of talinolol.

Results

In the in vitro study, incubation of Caco‐2 cell with DLX caused a concentration‐dependent increase in the accumulation of Rhd123. In the in vivo study, co‐administration of DLX increased the bioavailability of talinolol. The ratio (90% confidence intervals) of AUC0–60, AUC0–∞, and Cmax (talinolol alone versus talinolol plus DLX) were 0.87(0.77–1.06), 0.85(0.74–1.01), 0.87 (0.68–1.12).

Conclusion

Our results suggest that DLX could inhibit the function of P‐gp in vitro and in vivo, and caution should be exercised when DLX is to be co‐administered with drugs that are P‐gp substrate. Copyright © 2011 John Wiley & Sons, Ltd.
Attentional biases in clinical populations with alcohol use disorders: is co‐morbidity ignored?
Authors: Sinclair Julia M.A. , Nausheen Bina , Garner Matthew J. , Baldwin David S.
Published: February 2011

Objective

To identify how psychiatric co‐morbidity was identified and assessed, in studies of attentional bias in clinical samples of patients with alcohol use disorders (AUDs).

Design

Systematic review methodology was used to identify studies and abstract data on alcohol‐related attentional biases and measurement of psychiatric co‐morbidity.

Results

Seventeen papers were identified that met the criteria for inclusion. All but one study were in patients meeting criteria for alcohol dependence. In 10 of the 17 studies, either no mention or minimal statements were made pertaining to possible co‐morbid conditions (including other substance use): five excluded patients with psychiatric diagnoses, (variously defined), and two excluded patients on ‘psychotropic medication’. Slow response latencies to all word types were found in studies where co‐morbid conditions were not considered.

Conclusions

Despite the high prevalence of psychiatric pathology in patients with AUDs (particularly depression), and the acknowledged impact that this has on aetiology, presentation and outcome, psychiatric co‐morbidity has not been consistently measured or described in experimental studies on alcohol‐related attentional biases in clinical samples. In order to have an accurate appreciation of the role of attentional biases in patients with AUDs, there needs to be a consistent approach to measuring the co‐occurrence of other psychopathology. Further research is needed to assess the impact of co‐morbidities on attentional biases in AUDs, to enable the development of more targeted psychological and pharmacological treatments. Copyright © 2011 John Wiley & Sons, Ltd.
Inter‐ and Intra‐Regional Variability of Leaf Litter Breakdown in Reference Headwater Streams of Northern Spain: Atlantic versus Mediterranean Streams
Authors: Pérez Javier , Menéndez Margarita , Larrañaga Santiago , Pozo Jesús
Published: February 2011

The main goal of this study was to examine the natural variability of alder (Alnus glutinosa (L.) Gaertn.) leaf processing and explore its potentiality as a functional indicator to assess the ecological status of Spanish headwater streams. Breakdown of leaf litter was studied during autumn‐winter in reference headwater streams of two regions of northern Spain: the Basque Country (on the Atlantic) and Catalonia (on the Mediterranean). Spring experiments were also carried out in the Atlantic region in order to study seasonal changes. Leaf mass loss rates were slightly higher in Catalonian streams. Temperature was not the main factor for explaining differences between the two regions. In the Atlantic one, however, water temperature determined the spatial and seasonal variability of leaf litter processing. Because of the high natural variability in breakdown rates, our results highlight the difficulty in detecting moderate impairments on stream functioning through the analysis of leaf litter decomposition if this process is not accompanied by the study of other factors affecting it. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Long‐Term Dynamics of Microbial Biofilm Communities of the River Rhine with Special References to Ciliates
Authors: Ackermann Barbara , Esser Markus , Scherwaß Anja , Arndt Hartmut
Published: February 2011

The aim of this study was to quantify and qualify seasonal changes of all important components of a microbial biofilm community. We explored the development of the biofilm community structure on submerged glass slides for 15 months including all organisms from bacteria to macro‐invertebrates. Besides bacteria, heterotrophic flagellates were the most abundant biofilm component followed by ciliates, meiofauna organisms and algae. Most important were sessile choanoflagellates, peritrichous ciliates and some crustaceans. Ciliates and macrofauna were the most important components with regard to the total biovolume. The biofilm architecture was strongly influenced by extracellular structures produced by protozoans and macro‐invertebrates. Alterations within the biofilm community were mainly due to changes in abundances rather than in the composition except for heterotrophic flagellates and macro‐invertebrates. Biofilm organisms were dominated by planktivorous organisms exerting a strong grazing impact on the plankton organisms in this large river. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Daphnia Pre‐Exposed to Toxic Microcystis Exhibit Feeding Selectivity
Authors: Tillmanns Angeline R. , Burton Sara K. , Pick Frances R.
Published: February 2011

In this study, short term feeding experiments were used to determine if Daphnia, pre‐exposed to cyanobacteria, could avoid cyanobacteria through feeding selectively. The results show that Daphnia ambigua were capable of altering the proportion of a single – celled cyanobacterium (Microcystis aeruginosa) to a chlorophyte (Chlorella kessleri) of similar size and shape. Also, D. ambigua pre‐exposed for eight weeks to a toxic strain of M. aeruginosa were more successful at avoiding this strain than D. ambigua pre‐exposed to C. kessleri or to a non‐toxic strain of M. aeruginosa. These experimental results suggest that further investigations of Daphnia 's ability to influence the dominance of cyanobacterial strains in lakes are warranted. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Sequential measurements of glomerular filtration rate in conscious rats by a bolus injection of iodixanol and a single blood sample
Authors: Katayama Rieko , Watanabe Kanji , Yamagishi Norio , Abe Sumito , Satoh Hiroshi , Furuhama Kazuhisa
Published: February 2011

To estimate the glomerular filtration rate (GFR) sequentially in conscious rats, we validated a single‐blood‐sample method using a bolus injection of the nonionic contrast medium iodixanol as a tracer. First, to clarify basal age‐related GFR profiles, iodixanol was intravenously administered once weekly at 1500 mg kg−1 I to clinically healthy male F344 rats from 6 to 15 weeks of age. The blood sample was collected 120 min later, and serum iodixanol concentration was measured by HPLC. GFR values decreased gradually by 9 weeks, presumably due to rapidly increased body weights, and then remained constant from 10 weeks onward. When converting the GFR from body weight to body surface area, the reference range (40–60 ml min−1 m−2) in the latter was much more stable than that (6–11 ml min−1 kg−1) in the former. For nephropathy rats induced by cisplatin (3.75–7.5 mg kg−1, i.v., single dose), bromoethylamine hydrobromide (BEA, 250–500 mg kg−1, i.v., single dose) or puromycin aminonucleoside (PAN, 15 mg kg−1 day−1, s.c., 10 days), GFR decreased or tended to decrease before increasing in serum urea nitrogen (UN) and creatinine concentrations. Accordingly, serum UN and creatinine concentrations became elevated when the GFR decreased to 50–60% of the basal value. This method without urine collection contributes to the reduction of animal numbers because of repeated application to the same animals. Copyright © 2011 John Wiley & Sons, Ltd.
Low‐level chronic exposure to cadmium enhances the risk of long bone fractures: a study on a female rat model of human lifetime exposure
Authors: Brzóska Malgorzata M.
Published: February 2011

In the present paper, the hypothesis that low chronic exposure to cadmium (Cd) enhances the risk of long bone fractures was investigated in a female rat model simulating human lifetime exposure in non‐Cd‐polluted areas. For this purpose, the femur and both tibias of control female rats and those exposed to Cd (1 mg Cd l−1 in drinking water for 24 months since weaning) were assigned to geometric, densitometric (bone mineral content, BMC, and density, BMD), radiographic and biomechanical studies as well as assessing their chemical composition. The exposure to Cd disturbed mineralization (decreased BMD and minerals content, including calcium, magnesium, zinc, copper and iron) and weakened the biomechanical strength of the femur and tibia, enhancing their fragility. The Z‐score values for the BMD revealed osteopenia of the femur and tibia in 20 and 30% of the Cd‐exposed female rats, respectively, and osteoporosis in 80 and 70%, respectively. In 30% of the Cd‐exposed animals, femoral neck fracture was evident in the radiographic picture. The findings seem to confirm the hypothesis that a low exposure to Cd during the lifetime may be an important risk factor for osteoporosis and fractures of long bones, and especially for femoral neck fracture in elderly women. The results indicate that greater attention should be paid to Cd as an environmental risk factor for the increasing rate of osteoporosis and bone fractures in old population. Copyright © 2011 John Wiley & Sons, Ltd.