bluuebunny/crossref_metadata_2025 huggingface dataset:
Homochiral Oligopeptides via a Lattice‐Controlled Polymerisation in Racemic Crystals of Valine N‐Carboxyanhydride Suspended in Aqueous Solutions
Authors: Eliash Ran , Nery Jose G. , Rubinstein Irena , Clodic Gilles , Bolbach Gérard , Weissbuch Isabelle , Lahav Meir
Published: October 2007

As part of our program on the biochirogenesis of homochiral peptides, we report the formation of racemic parallel (p) β sheets composed of alternating R and S chains of up to 14–15 repeat units of the same handedness through the polymerisation of (R,S)‐valine N‐carboxyanhydride (NCA) crystals suspended in aqueous solutions of a primary amine as the initiator. The occurrence of such a lattice‐controlled reaction accompanied by a reduction in volume implies the operation of a mechanism that differs from that of the common solid‐state polymerisation in vinyl systems. The topotacticity of the reaction is explained through the operation of a multistep nonlinear process comprising lattice control coupled with an asymmetric induction in the formation of homochiral short peptides followed by their self‐assembly into racemic p β sheets, which operate as efficient templates in the ensuing process of enantioselective chain elongation at the polymer/crystal interface. The composition of the diastereoisomeric libraries of oligopeptides was determined by MALDI‐TOF and MALDI‐TOF‐TOF MS analyses of the products obtained from monomers enantioselectively labelled with deuterium. The structure of the p β sheets could be determined by initiating the polymerisation reaction with water‐soluble esters of enantiopure α‐amino acids or short peptides. The same reaction performed with the monomer crystals suspended in hexane yielded a complex mixture of diastereoisomeric oligopeptides, thus highlighting the indispensable role played by water in controlling the stereoselectivity of the reaction. By contrast, polymerisation of (R,S)‐leucine NCA crystals, with a different packing arrangement that presumably does not endorse the formation of periodic peptide templates, yielded, both in aqueous and hexane suspensions, libraries of peptides dominated by heterochiral diastereoisomers.
Ein Verfahren zur automatisierten Herstellung von Mikrodüsen aus Glaskapillaren zur Tropfenerzeugung
Authors: Harnisch J. , Irlinger F. , Lüth T.
Published: October 2007

Dieser Artikel beschreibt ein neuartiges Verfahren zur automatisierten Herstellung feiner Düsen aus Glaskapillaren. Es wird damit möglich, ohne optische Überwachung des Vorgangs sehr gut reproduzierbare Düsendurchmesser zu erhalten. Um Glaskapillaren an ihrem Ende mit einer feinen Düse zu versehen, existieren im Wesentlichen zwei Methoden: das aktive Langziehen des erhitzten Röhrchens und das kraftfreie Anschmelzen des Röhrchens, wobei sich der Innendurchmesser durch die Oberflächenspannung des verflüssigten Glases verengt. Speziell mit der letzteren Methode werden Düsen erzeugt, deren Kontur sich besonders zur Dosierung kleinster Flüssigkeitsmengen eignet. Um dabei einen definierten Düsendurchmesser zu erreichen, muss der Schmelzprozess zum richtigen Zeitpunkt angehalten werden. Im Folgenden wird ein Verfahren beschrieben, wie während des Schmelzprozesses das Erreichen des gewünschten Innendurchmessers automatisch erkannt werden kann, so dass eine serienmäßige Herstellung der Düsen ermöglicht wird. In Versuchen wurden Düsendurchmesser zwischen 35 und 200 μm aus Borosilikatglasröhrchen mit einem Außendurchmesser von 1,95 mm hergestellt. Diese Düsen dienen zur gezielten Dosierung von Tröpfchen aus Wasser, Polymeren und auch flüssigen Metallen, z. B. Lötzinn, mit einer Viskosität von etwa 1 – 40 mPas.
Zweidruck‐Batchdestillation zur Trennung homogener azeotroper Gemische
Authors: Klein A. , Repke J.‐U.
Published: October 2007

Im Rahmen dieser Arbeit wird der Einsatz des Zweidruckverfahrens im Batchbetrieb systematisch analysiert und diskutiert. Hierzu wird ein neu entwickeltes, experimentell validiertes rigoroses Modell, das das Anfahren aus dem kalten und leeren Zustand berücksichtigt, zur Durchführung der Simulationsstudie genutzt. Ein entscheidender Einflussfaktor ist das volumetrische Verhältnis von zu trennendem Gemisch zu Feedstrom. Die Ergebnisse lassen eine Auswahl der geeigneten Prozesskombination von regulärem und inversem Batchprozess für den Zweidruckbetrieb in Abhängigkeit der Feedkonzentration und Produktreinheiten zu. Es ergeben sich für das untersuchte homogene azeotrope Gemisch Konzentrationsbereiche, in denen mit dem inversen Prozess schneller und energetisch günstiger getrennt werden kann.
Prozessoptimierung: Methoden, Anwendungen und Herausforderungen
Authors: Li Pu
Published: October 2007

Eine immer wichtigere Rolle spielt die Prozessoptimierung in der modernen Industrie. In diesem Beitrag wird ein Überblick über neue Entwicklungen der wesentlichen Methoden zur Prozessoptimierung und ihre Anwendungen in der Chemieindustrie gegeben. Es handelt sich insbesondere um die wichtigsten Aspekte der Prozessoptimierung, nämlich die dynamische Optimierung großer Systeme, die Optimierung unter Unsicherheiten und die Echtzeitoptimierung. Darüber hinaus werden Ergebnisse aus eigenen Forschungsarbeiten in diesen Gebieten präsentiert, sowohl die methodische Entwicklung als auch die praktische Anwendung. Weiterhin werden die Herausforderungen und zukünftige Anwendungen der Prozessoptimierung diskutiert.
Optimierung des Betriebs einer Nebengewinnungsanlage in Bezug auf Verfahrenstechnik und Wirtschaftlichkeit durch Einsatz eines dynamischen Prozessmodells
Authors: Liszio P. , Thielert H. , Leuchtmann K. P. , Scheckreiter D.
Published: October 2007

Die Anwendung der chemischen Absorption als Verfahren der Luftreinhaltung ist Stand der Technik, jedoch stellen die steigenden Anforderungen an die Reinheit der Gasemissionen (TA‐Luft und Neufassungen) bei den gängigen Verfahren deren Wirtschaftlichkeit immer wieder zur Diskussion. Üblicherweise werden für Nebengewinnungsanlagen Prozessleitsysteme für die Anlagenautomatisierung eingesetzt. Diese Prozessleitsysteme sind in der Lage, Einzelregelungen durchzuführen, deren Vorgabe von den eingesetzten Bedienern kommt. Je nach Anlagenverständnis dieser Bediener wird die jeweilige Anlage gut oder schlecht gefahren. Mit Hilfe des Automatisierungsmodells GTC sind Betreiber von Kokereigasentschwefelungsanlagen in der Lage, die Vorgaben für die Einzelregelungen aus dem Modell GTC zu berechnen und an das Prozessleitsystem zu übertragen. Diese Vorgehensweise stellt sicher, dass die Vorgaben für die Einzelregler aufeinander abgestimmt sind und den betrieblichen Anforderungen entsprechen. Es wird am Beispiel der Kokereigasbehandlung TKS gezeigt wie das Modell GTC in den betrieblichen Prozess integriert wurde und wie die real gefundenen Messwerte mit den berechneten Messwerten übereinstimmten. Des Weiteren wird über die betriebliche Akzeptanz der Modelle berichtet.
Optimale Versuchsplanung in der chemischen Verfahrenstechnik
Authors: Arellano‐Garcia H. , Schöneberger J. , Körkel S.
Published: October 2007

Die Verwendung von Modellen für Designaufgaben, Prozessführung und Optimierung von Teilprozessen oder Gesamtanlagen ist zu einer gängigen Vorgehensweise in der Prozessindustrie geworden. Allerdings hängt die Qualität der Modellaussagen zur Beschreibung der zugrunde liegenden Phänomene von der Modellstruktur und von den Werten der enthaltenen Parameter ab, die im Rahmen einer Modellvalidierung unter Verwendung von experimentellen Daten anzupassen sind. Der Weg über die Parameteridentifikation durch Aufprägung von Störungen bzw. Sprungfunktionen ist eine weit verbreitete Methode insbesondere für Systeme, die durch lineare Modelle dargestellt werden. Für nichtlineare Systeme ist jedoch die Wahl der durchzuführenden Experimente im Hinblick auf die Festlegung der Modellstruktur, der Genauigkeit und der Zuverlässigkeit von Modellparametern sowie der Reduzierung des experimentellen Aufwandes ausschlaggebend. Die Entscheidung zur Durchführung von entsprechenden Experimenten stellt daher einen Kompromiss zwischen der Qualität der aufgenommenen Daten sowie Anzahl und Art der Experimente dar. Durch optimale Auslegung von Experimenten kann die Zuverlässigkeit der Schätzung maximiert werden. Dieser Beitrag beschreibt die Formulierung von Parameterschätz‐ und Versuchsplanungsproblemen, diskutiert Methoden zu deren numerischer Behandlung und demonstriert an einem Beispiel den erfolgreichen Einsatz der Methoden.
The Slow Molecular Mobility in Amorphous Trehalose
Authors: Moura Ramos Joaquim J. , Pinto Susana S. , Diogo Hermínio P.
Published: October 2007

The molecular mobility in amorphous trehalose is studied by thermally stimulated depolarisation currents (TSDC). The effect of aging on the sub‐Tg motional processes was analysed during annealing at a given aging temperature, some degrees below the calorimetric glass transition temperature Tg=115 °C. The features of different motional components of the secondary relaxation are monitored as a function of time as the glass structurally relaxes on aging. The faster components of the secondary relaxation are negligibly dependent on aging and may be ascribed to intramolecular modes of motion, while the slower motional modes show a significant dependence on aging consisting of some kind of local motions with some intermolecular nature. The dielectric strength of this relaxation decreases with increasing aging time, and there is no evidence for any modification with aging of the relaxation time of this local mobility. The TSDC study of the molecular mobility of amorphous trehalose in the temperature region of the glass transformation provides the unexpected result that no glass transition signal is observable in this temperature region.
Correlation between Na* Emission and “Chemically Active” Acoustic Cavitation Bubbles
Authors: Sunartio Devi , Yasui Kyuichi , Tuziuti Toru , Kozuka Teruyuki , Iida Yasuo , Ashokkumar Muthupandian , Grieser Franz
Published: October 2007

The emission from electronically excited sodium atoms (Na*) from aqueous solutions containing NaCl or sodium dodecylsulfate under ultrasonic irradiation is studied. Evidence is presented that strongly suggests Na* emission arises from a population of bubbles that are sonochemically active but not producing sonoluminescence (SL). Results indicate that the Na* emission intensity is mainly dependent on the concentration of Na+ ions near the bubble/solution interface. The results provide further insight into the origin of alkali metal spectral line emission from sonicated aqueous solutions containing sodium ions.
The microenvironment of the embryonic neural stem cell: Lessons from adult niches?
Authors: Lathia Justin D. , Rao Mahendra S. , Mattson Mark P. , ffrench‐Constant Charles
Published: October 2007

A better understanding of the signals regulating embryonic neural stem cells is clearly an important goal. However, many studies on neural stem cell biology are conducted on the slowly‐dividing cells found in the adult CNS, where specialized microenvironments or niches maintain the stem cells throughout life. By contrast, the embryonic VZ is a transient structure that does not fulfill the criteria conventionally used to define niches. In this review we will examine whether, despite these differences, the signals found in other adult stem cell niches are present in the VZ. Using the similarities and differences we observe, we will re‐consider whether the location of embryonic stem cell populations such as the VZ can be thought of as niches. Finally, we will ask how these lessons from the niche inform our understanding of neurodevelopmental diseases and cancers of the CNS. Developmental Dynamics 236:3267–3282, 2007. © 2007 Wiley‐Liss, Inc.
Characterization of the enigma family in zebrafish
Authors: Ott Elisabeth B. , Sakalis Philippe A. , Marques Ines J. , Bagowski Christoph P.
Published: October 2007

The three Enigma subfamily proteins, Enigma, Enigma homologue, and Cypher/ZASP belong to the PDZ and LIM encoding protein family, which is characterized by the presence of a PDZ‐ and one or more LIM domains. PDZ/LIM proteins play important biological roles, and all members have been shown to associate with the actin cytoskeleton. We describe here the splice form specific expression patterns for the three Enigma subfamily members during zebrafish embryogenesis. Whole‐mount in situ hybridization revealed common and distinct expression patterns for the different PDZ or LIM domain encoding splice variants. We further studied the role of enigma in zebrafish development. Enigma knockdown appeared to be embryonic lethal shortly after the end of gastrulation and in few surviving embryos led to elongation defects and disorganized somites. In summary, we show here the temporal and spatial expression patterns of the three Enigma family members and their PDZ and LIM domain encoding splice forms during zebrafish embryogenesis. Our results suggest that enigma is important for the formation and organization of somites and might play an important role for actin cytoskeleton organization during development. Developmental Dynamics 236:3144–3154, 2007. © 2007 Wiley‐Liss, Inc.
Correlation between recent thymic emigrants and CD31+ (PECAM‐1) CD4+ T cells in normal individuals during aging and in lymphopenic children
Authors: Junge Sonja , Kloeckener‐Gruissem Barbara , Zufferey Romain , Keisker Andre , Salgo Bettina , Fauchere Jean‐Claude , Scherer Franziska , Shalaby Tarek , Grotzer Michael , Siler Ulrich , Seger Reinhard , Güngör Tayfun
Published: October 2007

CD31+CD45RA+RO– lymphocytes contain high numbers of T cell receptor circle (TREC)‐bearing T cells; however, the correlation between CD31+CD4+ lymphocytes and TREC during aging and under lymphopenic conditions has not yet been sufficiently investigated. We analyzed TREC, telomere length and telomerase activity within sorted CD31+ and CD31– CD4+ lymphocytes in healthy individuals from birth to old age. Sorted CD31+CD45RA+RO– naive CD4+ lymphocytes contained high TREC numbers, whereas CD31+CD45RA–RO+ cells (comprising ⩽5% of CD4+ cells during aging) did not contain TREC. CD31+ overall CD4+ cells remained TREC rich despite an age‐related tenfold reduction from neonatal (100 : 1000) to old age (10 : 1000). Besides a high TREC content, CD31+CD45RA+RO–CD4+ cells exhibited significantly longer telomeres and higher telomerase activity than CD31–CD45RA+RO–CD4+ cells, suggesting that CD31+CD45RA+RO–CD4+ cells represent a distinct population of naive T cells with particularly low replicative history. To analyze the value of CD31 in lymphopenic conditions, we investigated six children after allogeneic hematopoietic stem cell transplantation (HSCT). Reemerging overall CD4+ as well as naive CD45RA+RO–CD4+ cells predominantly expressed CD31 and correlated well with the recurrence of TREC 5–12 months after HSCT. Irrespective of limitations in the elderly, CD31 is an appropriate marker to monitor TREC‐rich lymphocytes essentially in lymphopenic children after HSCT.
Human anti‐saliva immune response following experimental exposure to the visceral leishmaniasis vector, Lutzomyia longipalpis
Authors: Vinhas Vera , Andrade Bruno B. , Paes Fábio , Bomura Andréa , Clarencio Jorge , Miranda José C. , Báfica André , Barral Aldina , Barral‐Netto Manoel
Published: October 2007

Experiments in animals verified that phlebotomine saliva enhances Leishmania infection, and vaccination with saliva prevents disease. We have shown that individuals from an endemic area of visceral leishmaniasis displayed robust antibody responses to saliva from the vector Lutzomyia longipalpis, which correlated with anti‐parasite cell‐mediated immunity. Here, we explored human anti‐saliva responses following exposure to sand flies, using an in vivo bite model in which normal volunteers were exposed four times to 30 laboratory‐reared Lu. longipalpis. Following the third exposure, normal volunteers developed diverse dermatological reactions at the site of insect bite. Serum from normal volunteers displayed high levels of anti‐salivary gland sonicate IgG1, IgG4 and IgE as well as several salivary gland proteins. Furthermore, following in vitro stimulation with salivary gland sonicate, there was an increased frequency of CD4+CD25+ and CD8+CD25+ T cells as well as IFN‐γ and IL‐10 synthesis. Strikingly, 1 year after the first exposure, PBMC from the volunteers displayed recall IFN‐γ responses that correlated with a significant reduction in infection rates using a macrophage‐lymphocyte autologous culture. Together, these data suggest that human immunization against sand fly saliva is feasible and recall responses are obtained even 1 year after exposure, opening perspectives for vaccination in man.
New Mixed‐Metal Aggregates Derived From Dinickel Complexes on a 2‐Formylphenolate Template: Counteranion Dependent Formation of 1D Chain and Discrete NaNi2 Complexes
Authors: Paital Alok Ranjan , Mikuriya Masahiro , Ray Debashis
Published: October 2007

The combination of 2‐formylphenol (Hfp) and the dinucleating ligand H3L {2‐(2′‐hydroxyphenyl)‐1,3‐bis[4‐(2‐hydroxyphenyl)‐3‐azabut‐3‐enyl]‐1,3‐imidazolidine} with Ni(NO3)2·6H2O leads to the self‐assembly of a Ni2 complex capable of showing anion dependent Na+ coordination. The terminal aqua coordinated [Ni2(fp)L(H2O)]·3H2O (1·3H2O) neutral fragment, formed in the absence of any Na+ source, produces a 1D chain complex [{Ni2(fp)L(N3)(Na)(H2O)}·5H2O]n (2·5H2O)n and a discrete NaNi2 complex [Ni2(fp)L(Na)(H2O)2]·ClO4·H2O (3·ClO4·H2O) through its weak oxophilic interaction with a Na+ cation of the coordinated trisphenolate unit of L3– as observed in metallacrowns. In complexes 2 and 3, the NiII ions are coupled ferromagnetically to yield S = 2 ground states. The magnetic data can be modeled by using the Van Vleck equation incorporating intermolecular interactions. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
A Facile and Efficient Multi‐Gram Synthesis of N‐Protected 5‐(Guanidinocarbonyl)‐1H‐pyrrole‐2‐carboxylic Acids
Authors: Schmuck Carsten , Bickert Volker , Merschky Michael , Geiger Lars , Rupprecht Daniel , Dudaczek Jürgen , Wich Peter , Rehm Thomas , Machon Uwe
Published: October 2007

The synthesis of two versatile building blocks for supramolecular anion binding motifs, 5‐(N‐Boc‐guanidinocarbonyl)‐1H‐pyrrole‐2‐carboxylic acid (1) and 5‐(N‐Cbz‐guanidinocarbonyl)‐1H‐pyrrole‐2‐carboxylic acid (2) is reported. Using these building blocks, a guanidiniocarbonyl‐pyrrole anion binding site can easily be introduced into more complex molecules by using standard amide coupling conditions. Both syntheses can be performed on a multi‐gram scale. The products are obtained in pure form and can be stored as solids without decomposition. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
A Novel Flow‐Through Planar Solid Contact Sensor for the Determination of Lead with Potentiometric Anionic Response
Authors: Kamel Ayman H.
Published: October 2007

The construction and general performance characteristics of two poly(vinyl chloride) matrix chemical sensors for lead were described. These sensors were based on the use of ion association complexes of trihydroxoplumbate, [Pb(OH)3]− and tetraiodoplumbate, [PbI4]2−with cetylpyridinium chloride (CP) and iron(II)‐4,7‐bathophenanthroline [Fe(bphen)3]2+ as novel electroactive materials dispersed in o‐nitrophenyloctyl ether (o‐NPOE) plasticizer for ionometric sensor controls, respectively. The sensing membrane (3×5 mm) is immobilized on a wafer polyimide chip (size 13.5×3.5 mm) to offer a planar miniaturized design that could be easily used flow injection system. Under static modes of operation, the sensors revealed a near Nernstian response over a wide Pb2+ ion concentration range 7.9×10−7 to 10−4 and 3.2×10−7 to 10−4 mol L−1 with detection limit of 100 and 45.5 ng mL−1, respectively . In flow injection potentiometry, excellent reproducibility (RSD%=0.5%), fast response, high sensitivity, high sampling rate (50 sample h−1) and stable baseline was observed in the presence of 5×10−2 mol L−1 NaOH and 10−1 mol L−1 KI as a carrier for [CP][Pb(OH)3] and [Fe(bphen)3][PbI4] membrane based sensors, respectively. Validation of the assay method according to the quality assurance standards (range, within‐day repeatability, between‐day variability, standard deviation, accuracy, lower detection limit) reveals good performance characteristics and suggests application for routine determination of lead in industrial wastewaters and stack emissions of lead smelters. The results agree fairly well with data obtained by the standard atomic absorption methods.
Electrochemical Reduction of Ellman's Reagent: A Novel Selective Detection Protocol for Thiol Compounds
Authors: Scampicchio Matteo , Lawrence Nathan S. , Arecchi Alessandra , Mannino Saverio
Published: October 2007

Herein we detail a novel approach to the detection of total sulfhydryl thiol species based on an electrochemical adaptation of the classical Ellman's reaction. The ability to electrochemically reduce the nitro moieties of both the parent 5,5‐dithiobis(2‐nitrobenzoic acid) (DTNB) and the resulting 5‐thio‐2‐nitrobenzoic acid (TNBA) species provides a selective means of detecting thiol compounds. The use of the reductive sweep means that electrode passivation as a result of oxidative electrochemical procedures can be avoided and the selectivity improved through positioning the analytical signal within a region where few interferences reside. The electrochemical protocol enables the detection of the thiols in both acidic and basic media, which the colorimetric method is unable to do.
Electroanalytical Determination of Enrofloxacin in Reversed Phase HPLC
Authors: Sereno Silvia del C. , Sereno Leónides E. , Marioli Juan M.
Published: October 2007

The electrochemical behavior of a glassy carbon electrode is investigated towards the oxidation of enrofloxacin in aqueous solutions of different pH. Two oxidative waves are observed at a potential range from 0.70 V to 1.20 V (vs. SCE), the intensity of each depending on the pH of the solution. These results are used to set the parameters for the amperometric detection of enrofloxacin in HPLC analysis. A wide linear range and high sensitivity are obtained for a calibration plot using the optimized experimental conditions. The limit of detection (S/N=3) obtained using those conditions is approximately 0.2 pmol. The applicability of the methodology is demonstrated in the analysis of enrofloxacin in fortified milk samples.
Contribution of intercepted subsurface flow to road runoff and sediment transport in a logging‐disturbed tropical catchment
Authors: Negishi J. N. , Sidle R. C. , Ziegler A. D. , Noguchi S. , Rahim N. Abdul
Published: October 2007

Hydrological and sediment fluxes were monitored for a 1 yr period in a tropical headwater catchment where a 3 yr old logging road caused substantial Hortonian overland flow (HOF) and intercepted subsurface flow (ISSF). On a 51·5 m road section, ISSF became an increasingly important component of total road runoff, up to more than 90% for large storms. The proportion of ISSF contributed by road cuts along more or less planar slopes compared with ISSF from a zero‐order basin (convergent slopes) truncated by the road declined with increasing rainfall. During the monitored storms that generated ISSF along the road, on average, 28% of sediment export and 79% of runoff from the road section were directly attributable to ISSF. Estimates of total sediment export from the road surface (170 t ha−1 yr−1) and suspended sediment export from the logging‐disturbed catchment (4 t ha−1 yr−1) were exceptionally high despite 3 yr of recovery. ISSF caused not only additional road‐generated sediment export, but also exacerbated HOF‐driven erosion by creating a poor foundation for vegetation recovery on the road surface. Copyright © 2007 John Wiley & Sons, Ltd.
Methylenetetrahydrofolate reductase gene and risk of Alzheimer's disease in Koreans
Authors: Kim Jae‐Min , Stewart Robert , Kim Sung‐Wan , Yang Su‐Jin , Shin Il‐Seon , Shin Hee‐Young , Yoon Jin‐Sang
Published: October 2007

Background

The association between methylenetetrahydrofolate reductase (MTHFR) c.677C > T (A222V) polymorphism and Alzheimer's disease (AD) is controversial. The objectives of the study were to investigate the association between MTHFR c.677C > T polymorphism and AD in Korean elders and to the extent to which it is modified by the major components of one‐carbon metabolism and apolipoprotein E (APOE) genotype.

Methods

Seven hundred and thirty‐two community residents aged 65 or over were clinically assessed for AD. Genotyping was performed for MTHFR c.677C > T and APOE; serum levels of folate, vitamin B12, and homocysteine were assayed. Age, gender and education were included as covariates.

Results

A trend of association between TT genotype of MTHFR c.677C > T and AD was found [adjusted OR (95% CI): 1.73 (0.80–3.74)]. The association was significant in the presence of below‐median vitamin B12level [3.66 (1.14–11.71)] and in APOE e4 non‐carriers [2.97 (1.00–8.55)] with significant interaction terms, and bordered on significance in the presence of above‐median homocysteine level [2.73 (0.94–7.90)].

Conclusions

These findings suggest gene‐environment and gene‐gene interactions on the risk of AD in Koreans. Copyright © 2007 John Wiley & Sons, Ltd.
The effects of multifactorial fall prevention on depressive symptoms among the aged at increased risk of falling
Authors: Sjösten Noora M. , Vahlberg Tero J. , Kivelä Sirkka‐Liisa
Published: October 2007

Objectives

The aim was to determine the effects of multifactorial fall prevention on depressive symptoms among aged Finns at increased risk of falling.

Methods

This study is part of a multifactorial fall prevention trial with a randomised controlled design implemented in the town of Pori, western Finland. The study population consisted of ambulatory, 65‐year‐old or older Finns, with moderate or high cognitive and physical abilities who had fallen at least once during the previous 12 months. The participants (n = 591) were randomised into a risk‐based multifactorial fall prevention programme (intervention group, IG) or into a one‐time counselling group (control group, CG). The 1‐year intervention included individual geriatric assessment followed by treatment recommendations, individual guidance regarding fall prevention, physical exercise in small groups twice a month, psychosocial group activities and lectures once a month, home‐exercises and home hazard assessment. The outcome, depressive symptoms, was measured by the 30‐item Geriatric Depression Scale (GDS).

Results

The full GDS data with no missing items were available for 464 persons. A significant decrease in depressive symptoms during the 12‐month intervention was found both in IG and in CG, but the difference in change was not significant (p = 0.110). However, a significant difference in change between the groups was found among men and older subjects (≥75) in favour of the IG.

Conclusion

Multifactorial fall prevention had no effects on depressive symptoms among the community‐dwelling aged. However, men and older participants benefited from the intervention. Copyright © 2007 John Wiley & Sons, Ltd.
A forward application of age associated gray and white matter networks
Authors: Brickman Adam M. , Habeck Christian , Ramos Marco A. , Scarmeas Nikolaos , Stern Yaakov
Published: October 2007

To capture patterns of normal age‐associated atrophy, we previously used a multivariate statistical approach applied to voxel based morphometry that identified age‐associated gray and white matter covariance networks (Brickman et al. [2007]: Neurobiol Aging 28:284–295). The current study sought to examine the stability of these patterns by forward applying the identified networks to an independent sample of neurologically healthy younger and older adults. Forty‐two younger and 35 older adults were imaged with standard high‐resolution structural magnetic resonance imaging. Individual images were spatially normalized and segmented into gray and white matter. Covariance patterns that were previously identified with scaled subprofile model analyses were prospectively applied to the current sample to identify to what degree the age‐associated patterns were manifested. Older individuals were also assessed with a modified version of the Mini Mental State Examination (mMMSE). Gray matter covariance pattern expression discriminated between younger and older participants with high optimal sensitivity (100%) and specificity (90.5%). While the two groups differed in the degree of white matter pattern expression (t (75) = 5.26, P < 0.001), classification based on white matter expression was relatively low (sensitivity = 80% and specificity = 61.9%). Among older adults, chronological age was significantly associated with increased gray matter pattern expression (r (32) = 0.591, P < 0.001) but not with performance on the mMMSE (r (31) = −0.314, P = 0.085). However, gray matter pattern expression was significantly associated with performance on the mMMSE (r (31) = −0.405, P = 0.024). The findings suggest that the previously derived age‐associated covariance pattern for gray matter is reliable and may provide information that is more functionally meaningful than chronological age. Hum Brain Mapp 2008. © 2007 Wiley‐Liss, Inc.
Youth smoking, cigarette prices, and anti‐smoking sentiment
Authors: DeCicca Philip , Kenkel Donald , Mathios Alan , Shin Yoon‐Jeong , Lim Jae‐Young
Published: October 2007

In this paper, we develop a new direct measure of state anti‐smoking sentiment and merge it with micro‐data on youth smoking in 1992 and 2000. The empirical results from the cross‐sectional models show two consistent patterns: after controlling for differences in state anti‐smoking sentiment, the price of cigarettes has a weak and statistically, insignificant influence on smoking participation, and state anti‐smoking sentiment appears to have a potentially important influence on youth smoking participation. The cross‐sectional results are corroborated by results from the discrete time hazard models of smoking initiation that include state‐fixed effects. However, there is evidence of price‐responsiveness in the conditional cigarette demand by youth and young adult smokers. Copyright © 2007 John Wiley & Sons, Ltd.
Does age or life expectancy better predict health care expenditures?
Authors: Shang Baoping , Goldman Dana
Published: October 2007

It is an unresolved issue whether age or (expected) remaining life years better predicts health care expenditures. We first estimate a set of hazard models to predict life expectancy based on individual demographic characteristics and health conditions, and then use regression analyses to compare the predictive power of age and life expectancy in explaining health care expenditures. This paper differs from previous studies in that it uses predicted life expectancy to address the censoring of death; as a result, this paper goes beyond the large health care expenditures at the end of life and the results apply to both deceased and survivors. We find that age has little additional predictive power on health care expenditures after controlling for life expectancy, but the predictive power of life expectancy itself diminishes as health status measures are introduced into the model. These results are not of esoteric interest only for their statistical properties; we show that using life expectancy rather than age results in lower projections of future health care expenditures. This result suggests that increases in longevity might be less costly than models based on the current age profile of spending would predict. Copyright © 2007 John Wiley & Sons, Ltd.
Glycine N-methyltransferase−/− mice develop chronic hepatitis and glycogen storage disease in the liver
Authors: Liu Shih-Ping , Li Ying-Shiuan , Chen Yann-Jang , Chiang En-Pei , Li Anna Fen-Yau , Lee Ying-Hue , Tsai Ting-Fen , Hsiao Michael , Hwang Shiu-Feng , Chen Yi-Ming Arthur
Published: October 2007

Glycine N-methyltransferase (GNMT) affects genetic stability by regulating DNA methylation and interacting with environmental carcinogens. To establish a

Gnmt

knockout mouse model, 2 lambda phage clones containing a mouse

Gnmt

genome were isolated. At 11 weeks of age, the

Gnmt

−/− mice had hepatomegaly, hypermethioninemia, and significantly higher levels of both serum alanine aminotransferase and hepatic S-adenosylmethionine. Such phenotypes mimic patients with congenital

GNMT

deficiencies. A real-time polymerase chain reaction analysis of 10 genes in the one-carbon metabolism pathway revealed that 5,10-methylenetetrahydrofolate reductase, S-adenosylhomocysteine hydrolase (

Ahcy

), and formiminotransferase cyclodeaminase (

Ftcd

) were significantly down-regulated in

Gnmt

−/− mice. This report demonstrates that GNMT regulates the expression of both

Ftcd

and

Ahcy

genes. Results from pathological examinations indicated that 57.1% (8 of 14) of the

Gnmt

−/− mice had glycogen storage disease (GSD) in their livers. Focal necrosis was observed in male

Gnmt

−/− livers, whereas degenerative changes were found in the intermediate zones of female

Gnmt

−/− livers. In addition, hypoglycemia, increased serum cholesterol, and significantly lower numbers of white blood cells, neutrophils, and monocytes were observed in the

Gnmt

−/− mice. A real-time polymerase chain reaction analysis of genes involved in the gluconeogenesis pathways revealed that the following genes were significantly down-regulated in

Gnmt

−/− mice: fructose 1,6-bisphosphatase, phosphoenolpyruvate carboxykinase, and glucose-6-phosphate transporter.

Conclusion:

Because

Gnmt

−/− mice phenotypes mimic those of patients with

GNMT

deficiencies and share several characteristics with GSD Ib patients, we suggest that they are useful for studies of the pathogenesis of congenital

GNMT

deficiencies and the role of GNMT in GSD and liver tumorigenesis.
Gut-derived commensal bacterial products inhibit liver dendritic cell maturation by stimulating hepatic interleukin-6/signal transducer and activator of transcription 3 activity
Authors: Lunz John G. , Specht Susan M. , Murase Noriko , Isse Kumiko , Demetris Anthony J.
Published: October 2007

Intraorgan dendritic cells (DCs) monitor the environment and help translate triggers of innate immunity into adaptive immune responses. Liver-based DCs are continually exposed, via gut-derived portal venous blood, to potential antigens and bacterial products that can trigger innate immunity. However, somehow the liver avoids a state of perpetual inflammation and protects central immune organs from overstimulation. In this study, we tested the hypothesis that hepatic interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) activity increases the activation/maturation threshold of hepatic DCs toward innate immune signals. The results show that the liver nuclear STAT3 activity is significantly higher than that of other organs and is IL-6–dependent. Hepatic DCs in normal IL-6 wild-type (IL-6+/+) mice are phenotypically and functionally less mature than DCs from IL-6–deficient (IL-6−/−) or STAT3-inhibited IL-6+/+ mice, as determined by surface marker expression, proinflammatory cytokine secretion, and allogeneic T-cell stimulation. IL-6+/+ liver DCs produce IL-6 in response to exposure to lipopolysaccharide (LPS) and cytidine phosphate guanosine oligonucleotides (CpG) but are resistant to maturation compared with IL-6−/− liver DCs. Conversely, exogenous IL-6 inhibits LPS-induced IL-6−/− liver DC maturation. IL-6/STAT3 signaling influences the liver DC expression of toll-like receptor 9 and IL-1 receptor associated kinase-M. The depletion of gut commensal bacteria in IL-6+/+ mice with oral antibiotics decreased portal blood endotoxin levels, lowered the expression of IL-6 and phospho-STAT3, and significantly increased liver DC maturation.

Conclusion:

Gut-derived bacterial products, by stimulating hepatic IL-6/STAT3 signaling, inhibit hepatic DC activation/maturation and thereby elevate the threshold needed for translating triggers of innate immunity into adaptive immune responses. Manipulating gut bacteria may therefore be an effective strategy for altering intrahepatic immune responses. (Hepatology 2007.)
Antiangiogenic treatment with Sunitinib ameliorates inflammatory infiltrate, fibrosis, and portal pressure in cirrhotic rats
Authors: Tugues Sònia , Fernandez-Varo Guillermo , Muñoz-Luque Javier , Ros Josefa , Arroyo Vicente , Rodés Juan , Friedman Scott L. , Carmeliet Peter , Jiménez Wladimiro , Morales-Ruiz Manuel
Published: October 2007

Liver cirrhosis is a very complex disease in which several pathological processes such as inflammation, fibrosis, and pathological angiogenesis are closely integrated. We hypothesized that treatment with pharmacological agents with multiple mechanisms of action will produce superior results to those achieved by only targeting individual mechanisms. This study thus evaluates the therapeutic use of the multitargeted receptor tyrosine kinase inhibitor Sunitinib (SU11248). The

in vitro

effects of SU11248 were evaluated in the human hepatic stellate cell line LX-2 by measuring cell viability. The

in vivo

effects of SU11248 treatment were monitored in the livers of cirrhotic rats by measuring angiogenesis, inflammatory infiltrate, fibrosis, α-smooth muscle actin (α-SMA) accumulation, differential gene expression by microarrays, and portal pressure. Cirrhosis progression was associated with a significant enhancement of vascular density and expression of vascular endothelial growth factor-A, angiopoietin-1, angiopoietin-2, and placental growth factor in cirrhotic livers. The newly formed hepatic vasculature expressed vascular cellular adhesion molecule 1 and intercellular adhesion molecule 1. Interestingly, the expression of these adhesion molecules was adjacent to areas of local inflammatory infiltration. SU11248 treatment resulted in a significant decrease in hepatic vascular density, inflammatory infiltrate, α-SMA abundance, LX-2 viability, collagen expression, and portal pressure.

Conclusion:

These results suggest that multitargeted therapies against angiogenesis, inflammation, and fibrosis merit consideration in the treatment of cirrhosis. (Hepatology 2007.)
Transfer of suppressor of cytokine signaling 3 by an oncolytic adenovirus induces potential antitumor activities in hepatocellular carcinoma
Authors: Cui Qiang , Jiang Wei , Wang Yingxin , Lv Chen , Luo Jingjing , Zhang Wei , Lin Fang , Yin Yuexiang , Cai Rong , Wei Ping , Qian Cheng
Published: October 2007

The constitutive activation of signal transducer and activator of transcription 3 (STAT3) participates in carcinogenesis through up-regulation of genes encoding apoptosis inhibitors and cell cycle regulators, such as Bcl-xL, cyclins D1 and D2, and c-myc. Suppressor of cytokine signaling 3 (SOCS3) is one of the negative regulators of cytokine signaling and is frequently silenced in diverse cancers. In this study, we explored whether restoration of SOCS3 by oncolytic adenoviral vectors could inhibit the constitutive activation of the Janus kinase/STAT pathway and suppress tumor growth. Our data showed that SOCS3 was down-expressed in all liver tumor cell lines. The incorporation of SOCS3 or SOCS3 fused with cell-penetrating peptides (cpp-SOCS3) did not alter adenoviral replication selectively in liver tumor cells. The infection of cells with adenovirus CN305 (AdCN305)–SOCS3 and AdCN305-cpp-SOCS3 resulted in dramatic cytotoxicity in liver tumor cells. However, no cytotoxic effect was observed in normal cells infected with these vectors. Infection of liver tumor cells with AdCN305-SOCS3 and AdCN305-cpp-SOCS3 resulted in nearly complete inhibition of STAT3 phosphorylation and down-regulation of cyclin D1 and Bcl-xL. Treatment of the established tumor by AdCN305-SOCS3 and AdCN305-cpp-SOCS3 caused significant suppression of tumor growth. The suppression of tumor growth was due to the inhibition of STAT3 phosphorylation and induction of tumor cell death.

Conclusion:

This study suggests that transfer of SOCS3 by an oncolytic adenovirus represents a potent approach for cancer therapy. (Hepatology 2007.)
Snow‐distribution and melt modelling for glaciers in Zackenberg river drainage basin, north‐eastern Greenland
Authors: Mernild Sebastian H. , Liston Glen E. , Hasholt Bent
Published: October 2007

A physically based snow‐evolution modelling system (SnowModel) that includes four sub‐models: MicroMet, EnBal, SnowPack, and SnowTran‐3D, was used to simulate eight full‐year evolutions of snow accumulation, distribution, sublimation, and surface melt from glaciers in the Zackenberg river drainage basin, in north‐east Greenland. Meteorological observations from two meteorological stations were used as model inputs, and spatial snow depth observations, snow melt depletion curves from photographic time lapse, and a satellite image were used for model testing of snow and melt simulations, which differ from previous SnowModel tests methods used on Greenland glaciers. Modelled test‐period‐average end‐of‐winter snow water equivalent (SWE) depth for the depletion area differs by a maximum of 14 mm w.eq., or ∼6%, more than the observed, and modelled test‐period‐average snow cover extent differs by a maximum of 5%, or 0·8 km2, less than the observed. Furthermore, comparison with a satellite image indicated a 7% discrepancy between observed and modelled snow cover extent for the entire drainage basin. About 18% (31 mm w.eq.) of the solid precipitation was returned to the atmosphere by sublimation. Modelled mean annual snow melt and glacier ice melt for the glaciers in the Zackenberg river drainage basin from 1997 through 2005 (September–August) averaged 207 mm w.eq. year−1 and 1198 mm w.eq. year−1, respectively, yielding a total averaging 1405 mm w.eq. year−1. Total modelled mean annual surface melt varied from 960 mm w.eq. year−1 to 1989 mm w.eq. year−1. The surface‐melt period started between mid‐May and the beginning of June and lasted until mid‐September. Annual calculated runoff averaged 1487 mm w.eq. year−1 (∼150 × 106 m3) (1997–2005) with variations from 1031 mm w.eq. year−1 to 2051 mm w.eq. year−1. The model simulated a total glacier recession averaging − 1347 mm w.eq. year−1 (∼136 × 106 m3) (1997–2005), which was almost equal to previous basin average hydrological water balance storage studies − 244 mm w.eq. year−1 (∼125 × 106 m3) (1997–2003). Copyright © 2007 John Wiley & Sons, Ltd.
A steady‐state analytical slope stability model for complex hillslopes
Authors: Talebi Ali , Troch Peter A. , Uijlenhoet Remko
Published: October 2007

This paper presents a steady‐state analytical hillslope stability model to study the role of topography on rain‐induced shallow landslides. We combine a bivariate continuous function of the topographic surface, a steady‐state hydrological model of hillslope saturated storage, and the infinite slope stability assumption to investigate the interplay between terrain characteristics, saturated storage within hillslopes and soil mechanics. We demonstrate the model by examining the stability of nine characteristic hillslope types (landform elements) with three different profile curvatures (concave, straight and convex) and three different plan shapes (convergent, parallel and divergent). For each hillslope type, the steady‐state saturated storage corresponding to given recharge rates is computed for three different average bedrock slope angles. On the basis of the infinite slope stability method, the factor of safety (FS) along the hillslopes is determined. Our results demonstrate that in the steep slopes, the least stable situation occurs in hillslopes with convergent plan shapes and concave length profiles, while the convex ones are more stable. In addition to testing our method for nine characteristic hillslope types, a general relationship between plan shape and profile curvature of landform elements and the factor of safety is derived for a pre‐defined hillslope length scale. Our results show that slope stability increases when profile curvature changes from concave to convex. In terms of plan shapes, changing from convergent to divergent, slope stability increases for all length profiles. However, we find that the effect of plan shape is more pronounced for convex length profiles. Overall, we demonstrate that, in addition to bedrock slope, hillslope shape as represented by plan shape and profile curvature is an important control on hillslope stability. Copyright © 2007 John Wiley & Sons, Ltd.
Hepatitis C virus and risk of non‐Hodgkin lymphoma in British Columbia, Canada
Authors: Spinelli John J. , Lai Agnes S. , Krajden Mel , Andonov Anton , Gascoyne Randy D. , Connors Joseph M. , Brooks‐Wilson Angela R. , Gallagher Richard P.
Published: October 2007

We investigated Hepatitis C virus (HCV) seropositivity and the risk of non‐Hodgkin lymphoma (NHL) in a population‐based case‐control study in British Columbia, Canada. Cases were aged 20–79, diagnosed between March 2000 and February 2004, and resident in greater Vancouver or Victoria. Cases with HIV or a prior transplant were excluded. Controls were chosen from the Client Registry of the British Columbia (BC) Ministry of Health, and were age/sex/region frequency matched to cases. Antibodies for HCV were measured in 795 cases and 697 control subjects. HCV seropositivity was 2.4% in cases and 0.7% in controls [odds ratio (OR) = 2.6, 95% confidence interval (CI) = 0.9–7.4]. A significantly elevated risk was observed for B‐cell lymphoma (OR = 2.9, 95%CI = 1.0–8.6). The highest risks were associated with diffuse large B‐cell lymphoma (OR = 7.3, 95%CI = 2.1–25.0) and marginal zone lymphoma (OR = 6.1, 95%CI = 1.1–33.9). Our results provide further evidence that HCV infection contributes to NHL risk. © 2007 Wiley‐Liss, Inc.
Dietary glycemic load, glycemic index and colorectal cancer risk: Results from the Netherlands Cohort Study
Authors: Weijenberg Matty P. , Mullie Patrick F.F. , Brants Henny A.M. , Heinen Mirjam M. , Goldbohm R. Alexandra , van den Brandt Piet A.
Published: October 2007

Since hyperinsulinemia is implicated in the development of colorectal cancer, determinants of serum insulin levels, like the glycemic load and the glycemic index of the diet, could influence cancer risk. Our objective was to evaluate whether a diet with a high glycemic load or glycemic index is associated with increased colorectal cancer risk. In the Netherlands Cohort Study, 120,852 subjects completed a food frequency questionnaire in 1986. After 11.3 years of follow‐up, 1,225 colon and 418 rectal cancer cases were available for analysis. A case–cohort approach was used to estimate multivariate adjusted rate ratios and 95% confidence intervals for quintiles of energy‐adjusted glycemic load and glycemic index. The RR for colorectal cancer comparing the highest versus the lowest quintile levels of glycemic load and glycemic index were 0.83 (95% CI: 0.64–1.08) and 0.81 (95% CI: 0.61–1.08) for men and 1.00 (95% CI: 0.73–1.36) and 1.20 (95% CI: 0.85–1.67) for women. In general, no clear associations with cancer subsites were observed. Glycemic load and glycemic index were borderline significantly associated with an increased risk of proximal colon cancer in women (p‐trend = 0.06 and 0.08, respectively), however, these associations were attenuated after exclusion of the first 2 years of follow‐up (p‐trend = 0.165 and 0.254, respectively). In men, glycemic index was associated with a reduced risk of distal colon cancer (p‐trend = 0.03). Overall, our findings do not support the hypothesis that a diet with a high glycemic load or index is associated with a higher risk of colorectal cancer. © 2007 Wiley‐Liss, Inc.