bluuebunny/crossref_metadata_2025 huggingface dataset:
Ajoene exerts potent effects in 3T3‐L1 adipocytes by inhibiting adipogenesis and inducing apoptosis
Authors: Ambati Suresh , Yang Jeong‐Yeh , Rayalam Srujana , Park Hea Jin , Della‐Fera Mary Anne , Baile Clifton A.
Published: December 2008

This paper describes effects of several sulfur‐containing compounds from garlic on the cell viability, apoptosis and adipogenesis in 3T3‐L1 adipocytes. In both preadipocytes and mature adipocytes, 100 and 200 µM ajoene significantly decreased cell viability and increased apoptosis. The effect on apoptosis was further confirmed with Hoechst staining. In contrast, diallyl sulfide, diallyl disulfide, diallyl trisulfide, deoxyalliin, and allyl methyl sulfide had no significant effect on cell viability or apoptosis in either preadipocytes or mature adipocytes. In maturing preadipocytes ajoene significantly decreased lipid accumulation in a dose‐dependent manner and these results were further confirmed by a decrease in lipid droplet number and lipid content through Oil Red O staining. There was no significant change in lipid accumulation in maturing preadipocytes treated with other garlic derivatives. Thus, despite the same source of origin, garlic, ajoene was the only one with potent effects on cell viability, apoptosis and adipogenesis in 3T3‐L1 adipocytes. Copyright © 2008 John Wiley & Sons, Ltd.
The functional assessment ofAlpinia priceion metabolic syndrome induced by sucrose‐containing drinking water in mice
Authors: Chou Yi‐Chun , Wang Sheng‐Yang , Chen Gou‐Chun , Lin Yu‐Shen , Chao Pei‐Min
Published: December 2008

This study was designed to test whetherAlpinia pricei(AP), a member of the ginger family indigenous to Taiwan, reduced metabolic syndrome induced by sucrose‐containing drinking water in C57BL/6J mice. Mice given a chow diet were divided into a control group (C) or a test group given 30% sucrose water (SW) to drinkad libitum. After 22 weeks, mice in the SW group were subdivided into SW and SW + AP groups, the latter receiving a chow diet with an ethanol extract of AP (1500 mg/kg dosage). Four weeks later, bio‐indexes associated with metabolic syndrome were measured. Compared with the C group, the SW group had significantly higher body weight, visceral fat weights, serum and tissue lipid, serum insulin level and the area under the curve for blood glucose of the insulin tolerance test (p< 0.05). These indicators in the SW + AP group were lower than in the SW group except for serum lipid, although slightly higher than the C group. The SW + AP group also showed significantly lower serum levels of leptin and tumor necrosis factor‐αand a significantly higher level of adiponectin than the SW group. These results indicated that visceral adiposity and insulin resistance induced by sucrose water drinking might be alleviated by AP supplementation. Copyright © 2008 John Wiley & Sons, Ltd.
GeoSec: quarantine zones for mobile ad hoc networks
Authors: König André , Hollick Matthias , Krop Tronje , Steinmetz Ralf
Published: December 2008

With their wireless and infrastructureless nature, mobile ad hoc networks offer new possibilities for communication, but also new possibilities for attacks. An intrusion detection system combined with intrusion response mechanisms is a promising approach which mitigates the effects of attacks, but cannot be taken directly from wired or infrastructure‐based environments. In this paper, we propose an intrusion response mechanism for mobile ad hoc networks that excludes detected adversaries from the network based on their geographical position. To this end, we establish geographical quarantine zones, which block communication around misbehaving nodes. Thus, we depart from the assumption that attacks can be uniquely bound to addresses. Without loss of generality, we show how our approach can be used together with the AODV routing protocol to provide an intrusion response to a combination of Blackhole and Sybil attacks. In a series of simulation studies, we compare our approach with a ‘traditional’, address‐based intrusion response strategy. Copyright © 2008 John Wiley & Sons, Ltd.
A secure virtual point of service for purchasing digital media content over 3G wireless networks
Authors: Di Crescenzo Giovanni , Morera Raquel , Vakil Faramak , Varma Vijay K.
Published: December 2008

We propose the notion of a Secure Virtual Point of Service (SVPOS) as a network‐centric transaction server that facilitates the enhancement of 3G cell phones with a ‘mobile wallet’ capability allowing 3G subscribers to use their cell phones (or, in fact, other preferred mobile gadgets) for their daily transactions and payments. This paper shows how to design an SVPOS and an associated operator/subscriber/merchant protocol for purchasing digital media content over 3G networks. The resulting protocol guarantees a number of desirable privacy and security properties, such as privacy/anonymity of 3G subscribers (i.e. no identities, credit information or credit card numbers are revealed by subscriber to merchants), and protection of 3G operator, merchant, subscriber against various types of malicious behaviour, including transaction repudiation. The proposed SVPOS is ‘built’ on top of the Hypertext Transfer Protocol (HTTP), utilizes the 3rd Generation Partnership Project (3GPP) Generic Authentication Architecture (GAA) for subscriber and merchant authentication, and has an implicit key distribution mechanism that easily provides necessary encryption keys for the novel non‐repudiation mechanism of SVPOS. It also sends the necessary records of the transactions to the accounting entity of the network for charging and billing through standard protocols (e.g. Parlay‐X). Copyright © 2008 John Wiley & Sons, Ltd.
Syntax, and semantics‐based signature database for hybrid intrusion detection systems
Authors: Barry Bazara I. A. , Chan H. Anthony
Published: December 2008

Signature‐based intrusion detection systems (IDSs) have the advantages of producing a lower false alarm rate and using less system resources compared to anomaly based systems. However, they are susceptible to obfuscation used by attackers to introduce new variants of the attacks stored in the database. Some of the disadvantages of signature‐based IDSs can be attributed to the fact that they are mostly purely syntactic and ignore the semantics of the monitored systems. In this paper, we present the design and implementation of a signature database that assists a Specification‐based IDS in a converged environment. Our design is novel in terms of considering the semantics of the monitored protocols alongside their syntax. Our protocol semantics awareness is based on the state transition analysis technique which models intrusions at a high level using state transition diagrams. The signature database is hierarchically designed to insure a balance between ease of use and fast retrieval in real time. The database prototype is tested against some implemented attacks and shows promising efficiency. Copyright © 2008 John Wiley & Sons, Ltd.
AuthoCast—a mobility‐compliant protocol framework for multicast sender authentication
Authors: Schmidt Thomas C. , Wählisch Matthias , Christ Olaf , Hege Gabriel
Published: December 2008

Mobility is considered a key technology of the next generation Internet and has been standardized within the IETF. Rapidly emerging multimedia group applications such as IPTV, massive mutliplayer games (MMORPGs) and video conferencing increase the demand for mobile group communication, but a standard design of mobile multicast is still awaited. The open problem poses significant operational and security challenges to the Internet infrastructure. This paper introduces a protocol framework for authenticating multicast sources (MSs) and securing their mobility handovers. Its contribution is twofold: at first, the current mobile multicast problem and solution spaces are summarized from the security perspective. At second, a solution to the mobile source authentication problem is presented that complies to IPv6 mobility signaling standards. Using an autonomously verifiable one‐way authentication based on cryptographically generated addresses, a common design is derived to jointly comply with the mobile any source and source specific multicast (SSM) protocols that are currently proposed. This light‐weight scheme smoothly extends the unicast enhanced route optimization for mobile IPv6 and adds only little overhead to multicast packets and protocol operations. Copyright © 2008 John Wiley & Sons, Ltd.
Aberration analysis of Cs‐corrector system with twin hexapoles and transfer lens doublet in scanning transmission electron microscope by simple ray tracing based on geometrical optics
Authors: Kawasaki Tadahiro , Ichihashi Mikio , Matsutani Takaomi , Kimura Yoshihide , Ikuta Takashi
Published: December 2008

Optical properties of scanning transmission electron microscopes with aberration correction systems, called Cs‐correctors, were simply calculated from the viewpoint of the geometrical optics. Here, we focused on the Cs‐corrector consisting of twin hexapoles and two round lenses. Although the above system has already been investigated theoretically and developed successfully, we attempted to interpret its properties by a simple ray tracing technique to understand them more intuitively. The aberrations on the Gaussian image plane of an objective lens were calculated. Analyses of the aberrations up to the fifth order indicated that hexapoles and round lenses could eliminate up to third‐order aberrations in the total optical system, including the objective lens, when these four elements are arranged properly. The fourth‐ and fifth‐order aberrations could also be suppressed by adding one and two round lenses, respectively. As these results agreed well with those of previous theoretical studies, our simple method is useful for designing an actual aberration correction system. Copyright © 2008 John Wiley & Sons, Ltd.
Mining extremely small data sets with application to software reuse
Authors: Jiang Yuan , Li Ming , Zhou Zhi‐Hua
Published: December 2008

A serious problem encountered by machine learning and data mining techniques in software engineering is the lack of sufficient data. For example, there are only 24 examples in the current largest data set on software reuse. In this paper, a recently proposed machine learning algorithm is modified for mining extremely small data sets. This algorithm works in a twice‐learning style. In detail, a random forest is trained from the original data set at first. Then, virtual examples are generated from the random forest and used to train a single decision tree. In contrast to the numerous discrepancies between the empirical data and expert opinions reported by previous research, our mining practice shows that the empirical data are actually consistent with expert opinions. Copyright © 2008 John Wiley & Sons, Ltd.
Traits underlying the capacity of ant colonies to adapt to disturbance and stress regimes
Authors: Linksvayer Timothy A. , Janssen Marco A.
Published: December 2008

How do groups of social agents organize themselves to cope with stress and disturbances? We address this question by looking at ant colonies. We review the suites of traits that allow ant species to adapt to different disturbance and stress regimes, and changes in these regimes. Low temperatures and low nest site and food resource availability are important stresses that affect ant abundance and distribution. Large‐scale habitat disturbances, such as fire, grazing and mining, and small‐scale disturbances that more directly affect individual colonies, such as predation, parasitism and disease, also affect ant abundance and distribution. We use functional groups to study the social and individual traits underlying different responses to temperature stress, large‐scale habitat disturbance and competition from other ants. Specific individual and colony traits, such as colony size, queen number and worker specialization, seem to underlie adaptation to various stress and disturbance regimes. Copyright © 2008 John Wiley & Sons, Ltd.
Schubert und Reuleaux – ein verpasster Paradigmenwechsel? – zum 200. Geburtstag von Johann Andreas Schubert (1808–1870)
Authors: Mauersberger Klaus
Published: December 2008

Leben und Werk von Johann Andreas Schubert bestechen durch eine überragende Universalität und Methodenvielfalt. Beeindruckend ist vor allem Schuberts Fächerspektrum an seiner langjährigen Wirkungsstätte, der Kgl. Polytechnischen Schule zu Dresden; es reicht von der Mathematik und technischen Mechanik über die Maschinenkunde bis hin zum Straßen‐ und Wasserbau sowie zum Eisenbahn‐ und Brückenbau. Beeinflusst durch sein erfolgreiches Mitwirken an den Kommissionsentwürfen für die großen vogtländischen Eisenbahnviadukte leitete Schubert um 1850 einen Lehrgebietswechsel zum Baufach ein, dem er bis zu seinem Lebensende nachgehen sollte. Wenig bekannt ist die Tatsache, dass sich auch Franz Reuleaux, der wohl bekannteste und umstrittenste deutsche Maschinenwissenschaftler des ausgehenden 19. Jahrhunderts auf Schuberts vakant gewordene Professur im Maschinenfach beworben hatte. Anhand des verwickelten Berufungsvorganges soll Fragen des Paradigmenwechsels in den Technikwissenschaften sowie der Wechselwirkungen zwischen Bau‐ und Maschinenmechanik nachgegangen werden.
ISTA13‐catecholamine toxicity and metabolism in the ciliated protozoan,Tetrahymena pyriformis
Authors: Ud‐Daula Asad , Pfister Gerd , Schramm Karl‐Werner
Published: December 2008

A high throughput culture methodology of unicellular eukaryoteTetrahymena pyriformis, strain GL were used for the determination of catecholamines toxicity and their metabolism. Catecholamines exhibited acute toxicity toTetrahymenacells where dopamine andL‐DOPA showed higher toxic potential of EC10(0.39 and 0.63 mg/L, respectively) and EC20(1.1 and 1.0 mg/L, respectively). All the testing catecholamines were highly degradable in the PPY‐medium due to the oxidizing environment during incubation. They were also naturally synthesized and released byTetrahymenacells into the culture medium and increasingly accumulated with time where as noradrenalin demonstrated significant results. Cells were exposed with physiological concentration (0.12 mg/L) and one higher concentration (8.0 mg/L) of catecholamines, resulting noradrenalin depletion andin vivogeneration of a metabolite in response to dopamine with higher concentration treatment. This dopamine metabolite was relatively nonpolar compared with the catecholamines and was eluted later from the reverse phase C‐18 column. © 2008 Wiley Periodicals, Inc. Environ Toxicol, 2009.
Perfluorooctanoic acid alters T lymphocyte phenotypes and cytokine expression in mice
Authors: Son Hee‐Young , Lee Soyoung , Tak Eun‐Nam , Cho Hae‐Sung , Shin Hong‐In , Kim Sang‐Hyun , Yang Jae‐Ho
Published: December 2008

Perfluorooctanoic acid (PFOA) has been used in commercial applications and detected in environmental matrices. This study focuses on whether PFOA affects the function of immune organs (spleen and thymus). Male ICR mice were exposed to 0, 2, 10, 50, and 250 ppm of PFOA in drinking water for 21 days. PFOA differently altered T lymphocyte populations. In the spleen, all doses of PFOA decreased CD8+ lymphocytes; CD4+ lymphocytes were increased by 50 and 250 ppm of PFOA. Exposure to 250 ppm of PFOA increased CD8+ lymphocytes in the thymus. In the histopathological evaluation, the spleen of 250 ppm PFOA‐treated groups revealed the increase of lymphoid hyperplasia of white pulp without significant alteration of red pulp. The thymus of 250 ppm PFOA‐treated group showed decreased thickness of the cortex and medulla, but lymphoid cells were more densely arranged. PFOA elevated the expression of proinflammatory cytokines (tumor necrosis factor α, interleukin‐1β, and interleukin‐6) in the spleen, and proto‐oncogene, c‐myc, in the spleen and thymus. In conclusion, our data demonstrated that PFOA has an immunomodulatory effect by altering T lymphocyte phenotypes and gene expression of proinflammatory cytokines. © 2008 Wiley Periodicals, Inc. Environ Toxicol, 2009.
Immunological pattern alteration in shoe, hide, and leather industry workers exposed to hexavalent chromium
Authors: Mignini Fiorenzo , Tomassoni Daniele , Traini Enea , Vitali Mario , Scuri Stefania , Baldoni Emilia , Grappasonni Iolanda , Cocchioni Mario
Published: December 2008

Objective. The aim of this work was to assess the effects of hexavalent chromium [Cr(VI)] on shoe, leather, and hide industry workers, based on the assumption that Cr(VI) can behave as an environmental immunological “stressor.” Methods. The immunological patterns of 84 male subjects were studied in relation to Cr(VI) hematic and urinary levels. Cr(VI) was measured through atomic absorption. Lymphocyte subsets, mitogen‐mediated lymphocyte‐proliferation, cytokine levels, and natural killer (NK) cytotoxic activity were also assayed. Results. The urinary levels of the total amount of Cr(VI) were significantly higher in a subgroup of exposed subjects (group B) than in the control or in the lower exposed (group A). In group B, Cr(VI) caused a decrease in the density of glucocorticoid receptors (GR) on peripheral blood mononuclear cells (PBMC) and a increase of IL‐6. Cr(VI) did not modify NK‐mediated cytotoxicity, the plasmatic levels of inflammatory cytokines and related soluble receptors, and prostaglandin levels, while it tended to increase lymphocyte sensitivity to mitogens and the production of immunomodulant cytokines (IFN‐γ, IL‐4, and IL‐2). The experimental addition of Cr(VI) to the in vitro lymphocyte culture determined a significant inhibition of phagocytosis percentage, index, and killing percentage. These effects were neutralized by exogenous IFN‐γ. Conclusion. Cr(VI) could represent an environmental immunological stressor whose effects can be evaluated through laboratory surveys. The lymphocyte mitogen‐induced proliferation, GR receptor on PBMC, and IL‐6 plasma levels may represent a discriminating element between Cr(VI)‐induced stress and other kinds of stress. © 2008 Wiley Periodicals, Inc. Environ Toxicol, 2009.
Towards life long learning: three models for ubiquitous applications
Authors: Holzinger Andreas , Nischelwitzer Alexander , Friedl Silvia , Hu Bo
Published: December 2008

In this paper, we present three experimental proof‐of‐concepts: first, we demonstrate a ubiquitous computing framework (UCF), which is a network of interacting technologies that support humans ubiquitously. We then present practical work based on this UCF framework: TalkingPoints, which was originally developed for use at trading fairs in order to identify each participant and companyviatransponder and provide specific information during and after use. Finally, we propose GARFID, a concept for using advanced technologies for teaching young children. The main outcome of this research is that the concept of UCF raises a lot of possibilities, which can bring value and benefits for end‐users. When one follows the working‐is‐learning paradigm, it can be seen that the implementation of this type of technology can support life long learning (LLL), thereby providing evidence that technology can benefit everybody and make life easier. Copyright © 2008 John Wiley & Sons, Ltd.
Physical and Electrical Performance of Vapor–Solid Grown ZnO Straight Nanowires
Authors: Li JY , Li H
Published: December 2008

Physical and electrical properties of wurtzitic ZnO straight nanowires grown via a vapor–solid mechanism were investigated. Raman spectrum shows four first-order phonon frequencies and a second-order Raman frequency of the ZnO nanowires. Electrical and photoconductive performance of individual ZnO straight nanowire devices was studied. The results indicate that the nanowires reported here are n-type semi-conductors and UV light sensitive, and a desirable candidate for fabricating UV light nanosensors and other applications.
The Theory of General Economic Equilibrium
Authors: Mas-Colell Andreu
Published: December 2008

Andreu Mas-Colell has been doing pioneering work using differential topology in the analysis of general equilibrium. This work is regarded as outstanding and one of the major contributions to the development of rigorous economic theory in the last twenty years. The articles he has written have been difficult and technically demanding. In this book he brings this work together to show its scope and its power. He presents the analysis in a way which makes it accessible to the broader range of economic theorists and advanced students. This book has been long awaited as a seminal contribution to the subject.
Population Issues in Social Choice Theory, Welfare Economics, and Ethics
Authors: Blackorby Charles , Bossert Walter , Donaldson David J.
Published: December 2008

This book presents an exploration of the idea of the common or social good, extended so that alternatives with different populations can be ranked. The approach is, in the main, welfarist, basing rankings on the well-being, broadly conceived, of those who are alive (or ever lived). The axiomatic method is employed, and topics investigated include: the measurement of individual well-being, social attitudes toward inequality of well-being, the main classes of population principles, principles that provide incomplete rankings, principles that rank uncertain alternatives, best choices from feasible sets, and applications. The chapters are divided, with mathematical arguments confined to the second part. The first part is intended to make the arguments accessible to a more general readership. Although the book can be read as a defense of the critical-level generalized-utilitarian class of principles, comprehensive examinations of other classes are included.
Unusual location for Castleman's disease
Authors: Rao H G , Street I , Capper R
Published: December 2008

Objective:

We present the first reported case of persistent, posterior triangle lymphadenopathy in a child, caused by Castleman's disease.

Case report:

A seven-year-old boy presented with a painless swelling in the posterior triangle of his left neck, with no compression of the surrounding structures. A histological diagnosis of Castleman's disease was made. Eventual treatment was by complete excision. At six-month follow up, there were no signs of recurrence.

Conclusion:

The causes of persistent cervical lymphadenopathy in children are many. Most are not significant, but some are life-threatening. Castleman's disease should be considered as a possible diagnosis in persistent childhood lymphadenopathy.
Divine hiddenness and belief de re
Authors: CORDRY BENJAMIN S.
Published: December 2008

In this paper I argue that Poston and Dougherty's attempt to undermine the problem of divine hiddenness by using the notion of belief de re is problematic at best. They hold that individuals who appear to be unbelievers (because they are de dicto unbelievers) may actually be de re believers. I construct a set of conditions on ascribing belief de re to show that it is prima facie implausible to claim that seemingly inculpable and apparent unbelievers are really de re believers. Thus, while it is indeed possible that a de dicto unbeliever is a de re believer, it is unlikely that this has sufficiently general application to actual individuals to alleviate the problem of divine hiddenness.
Religion and Social Welfare in the Lebanon: Treating the Causes or Symptoms of Poverty?
Authors: JAWAD RANA
Published: December 2008

This article achieves two objectives. It introduces new insights to current thinking on social policy in the Middle East based on a case study of religious welfare in Lebanon. This in turn provides an analysis of how faith-based welfare may connect to social policy more broadly. Focusing on how five of the most prominent Lebanese Muslim and Christian welfare organisations engage with poverty reduction, the article draws attention to the moral dimension of social policy-making. This is illustrated by an analysis of how the Lebanese faith-based organisations (FBOs) define the objects of their interventions and, subsequently, how appropriately they respond to the causes of social problems. The analysis also includes a review of the FBOs' evaluation of their services. The overall argument of the article comments on the extent to which social welfare in Lebanon has scope to act beyond short-term, instrumental or politicised goals. It argues that human need, the ‘social case’ and poverty are three core concepts which determine the design of social interventions, but they also serve to confuse the definition of the object of social policy. The argument concludes that needs interpretation by welfare service providers in Lebanon is the site of deep contention in the policy-making process, since the lack of clarity in defining the object of policies can hamper the effectiveness of services. This means that while the social action undertaken by FBOs in Lebanon is more complex than the private or corporate charity initiatives known in the British or North American faith-based contexts, religious welfare programmes in Lebanon are more focused on palliative in-kind services.
Social Policy Digest Online
Authors: Bennett Fran , Jones Ken
Published: December 2008

The Social Policy Digest went online in May 2002, and since then has become a major resource on UK social policy issues. By the end of 2008 it contained well over 20,000 entries, covering policy developments and research findings across the whole range of social policy fields.
Wenn die Talsohle erreicht ist...
Authors: Turk Alexander J. , Russi Erich W.
Published: December 2008

Bei ungenügendem Ansprechen auf eine ausgebaute medikamentöse Therapie unter Einschluss einer Dauersauerstofftherapie zur Korrektur einer Hypoxämie kommen bei fortgeschrittener chronisch obstruktiver Lungenkrankheit (COPD) nur noch operative Maßnahmen wie eine Lungenvolumenreduktionsoperation (LVRS) oder eine Lungentransplantation als Therapieoptionen in Frage. Wie bei im Folgenden diskutierter Patientin, die durch ihre fortgeschrittene COPD invalidisiert war, kann man sich bei der Indikation für eine solche Therapie nicht immer auf Empfehlungen stützen, die auf kontrollierten Studien basieren. In einer solchen Grenzsituation wird aufgrund von Analogie-Schlüssen und klinischer Erfahrung bei gut informiertem Patient die Therapie-Entscheidung getroffen. Dieses Konzept hat sich glücklicherweise bei unserer Patientin, bei der eine chirurgische Volumenreduktion durchgeführt wurde, bewährt indem es zu einer frappanten subjektiven und objektiven Verbesserung durch den Eingriff kam.
Heimparenterale Ernährung oder Ernährung um zu leben
Authors: Keller Cornelia , Rühlin Maya , Ballmer Peter E. , Imoberdorf Reinhard
Published: December 2008

Anhand eines Fallbeispiels erläutern wir die Etablierung einer Heimparenteralen Ernährung (HPN) nach totaler Dünndarmresektion. Weil die totale parenterale Ernährung (TPN) mit schwerwiegenden Komplikationen wie katheter-assoziierter Sepsis und Thrombose, metabolischen Störungen und Leberversagen verbunden sein kann und zu eingreifenden Veränderungen der Lebensqualität (QoL) führt, ist eine umfassende, multidisziplinäre Betreuung und Schulung des Patienten Voraussetzung und führt zu einer signifikanten Reduktion katheterassoziierter Infektionen und zur Verbesserung der QoL. Obwohl in den letzten Jahren große Fortschritte in der Dünndarmtransplantation (SBTx) erzielt wurden, ist eine SBTx aufgrund des noch immer schlechteren Überlebens im Vergleich zur TPN nur im Falle eines TPN-Versagens indiziert.
Repräsentationaler Neglect und Arbeitsgedächtnis
Authors: Klos Thomas , Lorenz Robert , Reinhardt Frank
Published: December 2008

Der Zusammenhang zwischen repräsentationalem Neglect (RN) und Arbeitsgedächtnis wurde bei Patient JLA hinsichtlich des Abrufs von räumlich-geografischen und visuellen Informationen aus dem Gedächtnis untersucht. Der Patient erlitt einen rechtsseitigen fronto-temporo-parietalen Hirninfarkt und hatte einen leichten visuellen Neglect. Bei der Beschreibung eines öffentlichen Platzes zeigte JLA einen reproduzierbaren RN mit Blick aus Perspektive A. Bei mentaler Rotation um 180° bestand kein RN aus der Gegenperspektive B. Bei Beschreibung einer Wohnstrasse mit wenigen Objekten, zeigte der Patient auch nach Perspektivwechsel keinen RN. Eine vergleichbare Aufgabe mit mehr Items ergab bei Perspektivwechsel einen deutlichen RN. Die Gedächtnisdiagnostik zeigte Störungen im visuellen Arbeitsgedächtnis, die in Abhängigkeit von der Anzahl der Items variierten. Die verbalen Gedächtnisfunktionen waren leicht eingeschränkt.
Object Alternation in Alcohol Dependent Patients without Amnesic Syndrome
Authors: Brokate Barbara , Bernsdorff Karin , Braamhorst Wouter , Eling Paul , Hildebrandt Helmut
Published: December 2008

Several studies indicate that the frontal cortex is sensitive to the toxic effects of alcohol. Recent studies of our group revealed an impairment of alcohol dependent subjects in object alternation. One major problem of these studies is that they all used object alternation embedded in a spatial presentation and with two spatially arranged response buttons: a left and a right hand response key. The deficit in alternation tasks may be due to problems in processing these spatial features.

We investigated 24 detoxified alcohol dependent patients, who were in a long term treatment program, and 28 control subjects matched for intelligence and age, using a new object alternation paradigm avoiding confounding of spatial effects.

The results indicate that object alternation is impaired in long term alcohol dependent patients without amnesic syndrome, even when no differential spatial response is afforded. We suggest that internal control on a cognitive level, as well as on a behavioral level, may be a fundamental problem in addiction and might be related to ventromedial and orbitofrontal dysfunction.
On AGU's Position Statement, “Human Impacts on Climate”
Authors: Galvin Cyril
Published: December 2008

I respectfully dissent from the “Human Impacts on Climate” position statement adopted by AGU in December 2007 (Eos, 89(5), 41, 29 January 2008). According to the position statement, human activity has changed climate, “including the temperatures of the atmosphere, land, and ocean, the extent of sea ice and mountain glaciers, the sea level…” The statement also says, “The observed rapid retreat of Arctic sea ice is expected to continue and lead to the disappearance of summertime ice within this century.”
Member Input Sought to Ensure AGU's Continued Success
Authors: Grove Timothy L.
Published: December 2008

As an organization, AGU is indeed fortunate. Our Union has a growing membership worldwide with an average annual increase of 5.9% over the last 5 years. We are financially strong; we have planned carefully and managed our assets and our annual budgets so that we are able to navigate difficult times. Our Fall Meeting is “the” event for Earth and space scientists from more than 100 countries. Our publications continue to grow and evolve. Our outreach programs are gaining recognition in the communities we serve. Our development efforts are strengthening our ability to do more without taxing the revenues from meetings and publications. AGU is a preeminent scientific society.
The impact of circulating dendritic cells on the development and differentiation of thymocytes
Authors: Proietto Anna I , van Dommelen Serani , Wu Li
Published: December 2008

Central tolerance is established through the negative selection of self‐reactive thymocytes and the induction of T‐regulatory cells (T‐regs). A role for thymic epithelial cells in mediating both negative selection and T‐reg induction has been clearly shown. The role of thymic dendritic cells (DCs) in these processes has not been clearly determined but has been the focus of recent studies. Thymic DCs include two conventional DC (cDC) subtypes, CD8loSirpαhi/+ (CD8loSirpα+ herein) and CD8hiSirpαlo/− (CD8hiSirpα− herein). It has been shown that these DC subsets have distinct developmental origins, the CD8hiSirpα− cDCs developing intra‐thymically and the CD8loSirpα+ migrating into the thymus from the periphery. Furthermore, an important role for thymic DCs in the induction of T‐regs has been shown. In this review, the role of DCs in the development and education of T cells in the thymus will be reviewed, with emphasis on the role of circulatory DCs in mediating these processes.
Origins and tissue‐context‐dependent fates of blood monocytes
Authors: Varol Chen , Yona Simon , Jung Steffen
Published: December 2008

Peripheral blood monocytes play a central role in the mononuclear phagocyte system by providing a critical link between the bone marrow (BM), as major site of adult hematopoiesis, and peripheral, terminally differentiated mononuclear phagocyte populations, as represented macrophages and dendritic cells. Moreover, recent experimental evidence highlights the plasticity of these ephemeral mobile cells and their direct involvement in the establishment and resolution of inflammatory reactions. Here we summarize the recent advance in our understanding of monocyte origins, subset dynamics and monocyte fates. In particular, we will focus on emerging evidence for monocyte recirculation to the BM and discuss its potential implications in health and disease.
Exploring the mechanism of tryptophan 2,3-dioxygenase
Authors: Thackray Sarah J. , Mowat Christopher G. , Chapman Stephen K.
Published: December 2008

The haem proteins TDO (tryptophan 2,3-dioxygenase) and IDO (indoleamine 2,3-dioxygenase) are specific and powerful oxidation catalysts that insert one molecule of dioxygen into L-tryptophan in the first and rate-limiting step in the kynurenine pathway. Recent crystallographic and biochemical analyses of TDO and IDO have greatly aided our understanding of the mechanisms employed by these enzymes in the binding and activation of dioxygen and tryptophan. In the present paper, we briefly discuss the function, structure and possible catalytic mechanism of these enzymes.
Structures and reaction pathways of the molybdenum centres of sulfite-oxidizing enzymes by pulsed EPR spectroscopy
Authors: Enemark John H. , Astashkin Andrei V. , Raitsimring Arnold M.
Published: December 2008

SOEs (sulfite-oxidizing enzymes) are physiologically vital and occur in all forms of life. During the catalytic cycle, the five-co-ordinate square pyramidal oxo-molybdenum active site passes through the Mo(V) state, and intimate details of the structure can be obtained from variable frequency pulsed EPR spectroscopy through the hyperfine and nuclear quadrupole interactions of nearby magnetic nuclei. By employing variable spectrometer operational frequencies, it is possible to optimize the measurement conditions for difficult quadrupolar nuclei of interest (e.g. 17O, 33S, 35Cl and 37Cl) and to simplify the interpretation of the spectra. Isotopically labelled model Mo(V) compounds provide further insight into the electronic and geometric structures and chemical reactions of the enzymes. Recently, blocked forms of SOEs having co-ordinated sulfate, the reaction product, were detected using 33S (I=3/2) labelling. This blocking of product release is a possible contributor to fatal human sulfite oxidase deficiency in young children.
Iron acquisition by the haem-binding Isd proteins in Staphylococcus aureus: studies of the mechanism using magnetic circular dichroism
Authors: Tiedemann Michael T. , Muryoi Naomi , Heinrichs David E. , Stillman Martin J.
Published: December 2008

The bacterium Staphylococcus aureus is responsible for numerous hospital-acquired infections ranging from superficial wound lesions to more severe infections such as pneumonia, osteomyelitis and septicaemia and, in some cases, death. The Isd (iron-regulated surface determinant) proteins expressed by S. aureus and select other bacteria are anchored to the bacterial cell wall and membrane and are involved in extracting haem from haemoglobin as an iron source. Our knowledge of the overall haem-scavenging mechanism on the bacterial surface is limited. A detailed description of the haem-binding properties in the transport pathway is critical to our understanding of the mechanism for haem-iron scavenging in S. aureus. Our work involves using a combination of techniques to characterize both the dynamic and steady-state haem-binding properties of these proteins. UV–visible absorption and MCD (magnetic circular dichroism) spectroscopy provide diagnostic spectral data sensitive to the axial ligands, the spin state and oxidation state of the central haem-iron. Electrospray MS provides stoichiometric information on the numbers of haems bound, the effect of haem binding on the overall folding of each protein and kinetic information about the rate of haem binding. Together, these data allow us to address the outstanding questions regarding the mechanism of haem transport via the Isd protein chain in S. aureus.
Metalloregulatory proteins and nitric oxide signalling in bacteria
Authors: Spiro Stephen
Published: December 2008

Bacterial gene regulators containing transition metal cofactors that function as binding sites for small ligands were first described in the 1990s. Since then, numerous metal-containing regulators have been discovered, and our knowledge of the diversity of proteins, their cofactors and the signals that they sense has greatly increased. The present article reviews recent developments, with a particular focus on bacterial sensors of nitric oxide.
Time-resolved FTIR study of CO recombination with horseradish peroxidase
Authors: Maréchal Amandine , Ingledew W. John , Rich Peter R.
Published: December 2008

Vibrational changes associated with CO recombination to ferrous horseradish peroxidase were investigated by rapid-scan FTIR (Fourier-transform IR) spectroscopy in the 1200–2200 cm−1 range. At pH 6.0, two conformers of bound CO are present that appear as negative bands at 1905 and 1934 cm−1 in photolysis spectra. Their recombination rate constants are identical, confirming that they arise from two substates of bound CO that are in rapid thermal equilibrium, rather than from heterogeneous protein sites. A smaller positive band at 2134 cm−1 also appears on photolysis and decays with the same rate constant, indicative of an intraprotein geminate site involved in recombination or, possibly, a weak-affinity surface CO-binding site. Other signals arising from protein and haem in the 1700–1200 cm−1 range can also be time-resolved with similar kinetics.
Molecular architecture of the proton diode of cytochrome c oxidase
Authors: Brzezinski Peter , Reimann Joachim , Ädelroth Pia
Published: December 2008

CytcO (cytochrome c oxidase) is a membrane-bound multisubunit protein which catalyses the reduction of O2 to H2O. The reaction is arranged topographically so that the electrons and protons are taken from opposite sides of the membrane and, in addition, it is also linked to proton pumping across the membrane. Thus the CytcO moves an equivalent of two positive charges across the membrane per electron transferred to O2. Proton transfer through CytcO must be controlled by the protein to prevent leaks, which would dissipate the proton electrochemical gradient that is maintained across the membrane. The molecular mechanism by which the protein controls the unidirectionality of proton-transfer (cf. proton diode) reactions and energetically links electron transfer to proton translocation is not known. This short review summarizes selected results from studies aimed at understanding this mechanism, and we discuss a possible mechanistic principle utilized by the oxidase to pump protons.
Cytochrome c6A: discovery, structure and properties responsible for its low haem redox potential
Authors: Worrall Jonathan A.R. , Luisi Ben F. , Schlarb-Ridley Beatrix G. , Bendall Derek S. , Howe Christopher J.
Published: December 2008

Cytochrome c6A is a unique dithio-cytochrome of green algae and plants. It has a very similar core structure to that of bacterial and algal cytochromes c6, but is unable to fulfil the same function of transferring electrons from cytochrome f to Photosystem I. A key feature of cytochrome c6A is that its haem midpoint potential is more than 200 mV below that of cytochrome c6 (Em≈+340 mV) despite both cytochromes having histidine and methionine residues as axial haem-iron ligands. One salient difference between the haem pockets is that a valine residue in cytochrome c6A replaces a highly conserved glutamine residue in cytochrome c6. This difference has been probed using site-directed mutagenesis, X-ray crystallography and protein film voltammetry studies. It has been found that the stereochemistry of the glutamine residue within the haem pocket has a destabilizing effect and is responsible for tuning the haem's midpoint potential by over 100 mV. This large effect may have contributed to the evolution of a new biological function for cytochrome c6A.
Coherent Raman detected electron spin resonance spectroscopy of metalloproteins: linking electron spin resonance and magnetic circular dichroism
Authors: Bingham Stephen J. , Wolverson Daniel , Thomson Andrew J.
Published: December 2008

The simultaneous excitation of paramagnetic molecules with optical (laser) and microwave radiation in the presence of a magnetic field can cause an amplitude, or phase, modulation of the transmitted light at the microwave frequency. The detection of this modulation indicates the presence of coupled optical and ESR transitions. The phenomenon can be viewed as a coherent Raman effect or, in most cases, as a microwave frequency modulation of the magnetic circular dichroism by the precessing magnetization. By allowing the optical and magnetic properties of a transition metal ion centre to be correlated, it becomes possible to deconvolute the overlapping optical or ESR spectra of multiple centres in a protein or of multiple chemical forms of a particular centre. The same correlation capability also allows the relative orientation of the magnetic and optical anisotropies of each species to be measured, even when the species cannot be obtained in a crystalline form. Such measurements provide constraints on electronic structure calculations. The capabilities of the method are illustrated by data from the dimeric mixed-valence CuA centre of nitrous oxide reductase (N2OR) from Paracoccus pantotrophus.
Identification of genes targeted by microRNAs
Authors: Dalmay Tamas
Published: December 2008

miRNAs (microRNAs) are recently discovered regulators of gene expression. They target mRNAs that contain partially complementary sites to the miRNA. The level of complementarity is different between target site–miRNA pairs, and finding target genes has proved to be a bigger challenge than expected. The present paper reviews the different approaches to predict and experimentally identify genes targeted by miRNAs.
Role of miRNA-146a in the regulation of the innate immune response and cancer
Authors: Williams Andrew E. , Perry Mark M. , Moschos Sterghios A. , Larner-Svensson Hanna M. , Lindsay Mark A.
Published: December 2008

In mammalian cells, miRNAs (microRNAs) are the most abundant family of small non-coding RNAs that regulate mRNA translation through the RNA interference pathway. In general, it appears that the major function of miRNAs is in development, differentiation and homoeostasis, which is indicated by studies showing aberrant miRNA expression during the development of cancer. Interestingly, changes in the expression of miR-146a have been implicated in both the development of multiple cancers and in the negative regulation of inflammation induced via the innate immune response. Furthermore, miR-146a expression is driven by the transcription factor NF-κB (nuclear factor κB), which has been implicated as an important causal link between inflammation and carcinogenesis. In the present article, we review the evidence for a role of miR-146a in innate immunity and cancer and assess whether changes in miR-146a might link these two biological responses.
Regulation and function of Zip4, the acrodermatitis enteropathica gene
Authors: Andrews Glen K.
Published: December 2008

The SLC39A (solute carrier 39A) [ZIP (Zrt-Irt-like protein)] family consists of 14 members which are thought to control zinc uptake into the cytoplasm. Among these, ZIP4 is known to be particularly important for zinc homoeostasis. Mutations in this gene cause acrodermatitis enteropathica, a rare recessive-lethal human genetic disorder. In the present paper, our studies of the regulation and function of the mouse Zip4 gene are briefly reviewed. Mouse Zip4 is expressed at highest levels in tissues involved in absorption of dietary or maternal zinc, and the gene and protein are dynamically regulated by multiple post-transcriptional mechanisms in response to zinc availability. ZIP4 accumulates at the apical surface of enterocytes and endoderm cells when zinc is deficient, because of increased stability of the mRNA and stabilization of the protein. In contrast, when zinc is replenished, the mRNA is destabilized and the protein is internalized and degraded rapidly. The critical importance of ZIP4 in zinc homoeostasis is revealed in mice with targeted deletions of this gene. Homozygous Zip4-knockout embryos die during early morphogenesis and heterozygous offspring are significantly underrepresented and display an array of developmental defects, including exencephalia, anophthalmia and severe growth retardation. Mice heterozygous for Zip4-knockout are hypersensitive to zinc deficiency, which suggests that humans heterozygous for this gene may also be very sensitive to zinc deficiency.
Mechanism of the metal-mediated endocytosis of the prion protein
Authors: Hooper Nigel M. , Taylor David R. , Watt Nicole T.
Published: December 2008

The cellular form of the prion protein, PrPc, is critically required for the establishment of prion diseases, such as Creutzfeldt–Jakob disease. Within the N-terminal half of PrPc are four octapeptide repeats that bind Cu2+. Exposure of neuronal cells expressing PrPc to Cu2+ results in the rapid endocytosis of the protein. First, PrPc translocates laterally out of detergent-resistant lipid rafts into detergent-soluble regions of the plasma membrane, then it is internalized through clathrin-coated pits. The extreme N-terminal region of PrPc is critically required for its endocytosis, as is the transmembrane LRP1 (low-density lipoprotein receptor-related protein-1). Incubation of cells with a competitive inhibitor of LRP1 ligands, receptor-associated protein, or down-regulation of LRP1 with siRNA (short interfering RNA) reduces the endocytosis of PrPc. Zn2+ also promotes the endocytosis of PrPc, a phenomenon that is also dependent on the octapeptide repeats and requires LRP1.