bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding drug‐likeness
Authors: Ursu Oleg , Rayan Anwar , Goldblum Amiram , Oprea Tudor I.
Published: June 2011

‘Drug‐likeness’, a qualitative property of chemicals assigned by experts committee vote, is widely integrated into the early stages of lead and drug discovery. Its conceptual evolution paralleled work related to Pfizer's ‘rule of five’ and lead‐likeness, and is placed within this framework. The discrimination between ‘drugs’ (represented by a collection of pharmaceutically relevant small molecules, some of which are marketed drugs) and ‘nondrugs’ (typically, chemical reagents) is possible using a wide variety of statistical tools and chemical descriptor systems. Here we summarize 18 papers focused on drug‐likeness, and provide a comprehensive overview of progress in the field. Tools that estimate drug‐likeness are valuable in the early stages of lead discovery, and can be used to filter out compounds with undesirable properties from screening libraries and to prioritize hits from primary screens. As the goal is, most often, to develop orally available drugs, it is also useful to optimize drug‐like pharmacokinetic properties. We examine tools that evaluate drug‐likeness and some of their shortcomings, challenges facing these tools, and address the following issues: What is the definition of drug‐likeness and how can it be utilized to reduce attrition rate in drug discovery? How difficult is it to distinguish drugs from nondrugs? Are nondrug datasets reliable? Can we estimate oral drug‐likeness? We discuss a drug‐like filter and recent advances in the prediction of oral drug‐likeness. The heuristic aspect of drug‐likeness is also addressed. © 2011 John Wiley & Sons, Ltd. WIREs Comput Mol Sci 2011 1 760–781 DOI: 10.1002/wcms.52

This article is categorized under:

Computer and Information Science > Chemoinformatics
Relativistic Douglas–Kroll–Hess theory
Authors: Reiher Markus
Published: June 2011

Relativistic effects on molecular properties and energies are ubiquitous in chemistry. Their consideration in quantum chemical calculations requires Dirac's theory of the electron, whose application is not without obstacles. Douglas–Kroll–Hess theory accomplishes a decoupling of positive‐ and negative‐energy eigenstates of the Dirac one‐electron Hamiltonian by an expansion in the external potential. At low orders, this expansion already converges and provides efficient relativistic Hamiltonians to be used in routine quantum chemical calculations. The basic principles of the approach are reviewed, and most recent developments are discussed. © 2011 John Wiley & Sons, Ltd.

This article is categorized under:

Electronic Structure Theory > Ab Initio Electronic Structure Methods
Explicitly correlated electronic structure theory from R12/F12 ansätze
Authors: Ten‐no Seiichiro , Noga Jozef
Published: June 2011

Fundamental aspects of the explicitly correlated R12 and F12 theories are summarized in the perspective of recent advances related to our contribution in this field. Starting from the basics of pair functions and second quantized formulations, the R12/F12 ansätze have been applied to MP2, coupled‐cluster, and equation of motion coupled‐cluster theories. Emphasis is given to approaches that use the rational generator to create the exact cusp conditions (SP ansatz). Computational aspects of the evaluation of many‐electron integrals are also discussed in conjunction with the use of the Slater‐type geminal, which is the predominant choice for the correlation factor in modern R12/F12 theories. © 2011 John Wiley & Sons, Ltd.

This article is categorized under:

Electronic Structure Theory > Ab Initio Electronic Structure Methods
Global optimization
Authors: Hartke Bernd
Published: June 2011

The current status of global optimization in computational molecular science is characterized in this article by focusing on one particular area, evolutionary algorithms applied to cluster structure optimization. Other algorithms and application areas are also mentioned briefly, indicating a widespread use of global optimization techniques in every conceivable branch of computational molecular science. © 2011 John Wiley & Sons, Ltd. WIREs Comput Mol Sci 2011 1 879–887 DOI: 10.1002/wcms.70

This article is categorized under:

Structure and Mechanism > Molecular Structures
Paleoecology of mangroves along the Sibun River, Belize
Authors: Monacci Natalie M. , Meier-Grünhagen Ursula , Finney Bruce P. , Behling Hermann , Wooller Matthew J.
Published: June 2011

This study examines a sediment core (SR-63) from a mangrove ecosystem along the Sibun River in Belize, which is subject to both changes in sea-level and in the characteristics of the river's drainage basin. Radiocarbon dates from the core show a decreased sedimentation rate from ~ 6 ka to 1 cal ka BP and a marked change in lithology from primarily mangrove peat to fluvial-derived material at ~ 2.5 cal ka BP. Changes in the sedimentation rates observed in mangrove ecosystems offshore have previously been attributed to changes in relative sea-level and the rate of sea-level rise. Pollen analyses show a decreased abundance of Rhizophora (red mangrove) pollen and an increased abundance of Avicennia (black mangrove) pollen and non-mangrove pollen coeval with the decreased sedimentation rates. Elemental ratios ([N:C]a) and stable isotope analyses (δ15N and δ13C) show that changes in the composition of the organic material are also coeval with the change in lithology. The decrease in sedimentation rate at the site of core SR-63 and at offshore sites supports the idea that regional changes in hydrology occurred during the Holocene in Belize, influencing both mainland and offshore mangrove ecosystems.
Effect of adiposity on vitamin D status and the 25-hydroxycholecalciferol response to supplementation in healthy young and older Irish adults
Authors: Kirsty Forsythe L. , Livingstone M. Barbara E. , Barnes Maria S. , Horigan Geraldine , McSorley Emeir M. , Bonham Maxine P. , Magee Pamela J. , Hill Tom R. , Lucey Alice J. , Cashman Kevin D. , Kiely Mairead , Strain J. J. , Wallace Julie M. W.
Published: June 2011

There is increasing epidemiological evidence linking sub-optimal vitamin D status with overweight and obesity. Although increasing BMI and adiposity have also been negatively associated with the change in vitamin D status following supplementation, results have been equivocal. The aim of this randomised, placebo-controlled study was to investigate the associations between anthropometric measures of adiposity and the wintertime serum 25-hydroxycholecalciferol (25(OH)D) response to 15 μg cholecalciferol per d in healthy young and older Irish adults. A total of 110 young adults (20–40 years) and 102 older adults ( ≥ 64 years) completed the 22-week intervention with >85 % compliance. The change in 25(OH)D from baseline was calculated. Anthropometric measures of adiposity taken at baseline included height, weight and waist circumference (WC), along with skinfold thickness measurements to estimate fat mass (FM). FM was subsequently expressed as FM (kg), FM (%), FM index (FMI (FM kg/height m2)) and as a percentage ratio to fat-free mass (FFM). In older adults, vitamin D status was inversely associated with BMI (kg/m2), WC (cm), FM (kg and %), FMI (kg/m2) and FM:FFM (%) at baseline (r − 0·33, − 0·36, − 0·33, − 0·30, − 0·33 and − 0·27, respectively, all P values < 0·01). BMI in older adults was also negatively associated with the change in 25(OH)D following supplementation (β − 1·27, CI − 2·37, − 0·16, P = 0·026); however, no such associations were apparent in younger adults. Results suggest that adiposity may need to be taken into account when determining an adequate wintertime dietary vitamin D intake for healthy older adults residing at higher latitudes.
Chronic dietary supplementation of proanthocyanidins corrects the mitochondrial dysfunction of brown adipose tissue caused by diet-induced obesity in Wistar rats
Authors: Pajuelo David , Quesada Helena , Díaz Sabina , Fernández-Iglesias Anabel , Arola-Arnal Anna , Bladé Cinta , Salvadó Josepa , Arola Lluís
Published: June 2011

The present study aims to determine the effects of grape seed proanthocyanidin extract (GSPE) on brown adipose tissue (BAT) mitochondrial function in a state of obesity induced by diet. Wistar male rats were fed with a cafeteria diet (Cd) for 4 months; during the last 21 d, two groups were treated with doses of 25 and 50 mg GSPE/kg body weight. In the BAT, enzymatic activities of citrate synthase, cytochrome c oxidase (COX) and ATPase were determined and gene expression was analysed by real-time PCR. The mitochondrial function of BAT was determined in fresh mitochondria by high-resolution respirometry using both pyruvate and carnitine–palmitoyl-CoA as substrates. The results show that the Cd causes an important decrease in the gene expression of sirtuin 1, nuclear respiratory factor 1, isocitrate dehydrogenase 3γ and COX5α and, what is more telling, decreases the levels of mitochondrial respiration both with pyruvate and canitine–palmitoyl-CoA. Most of these parameters, which are indicative of mitochondrial dysfunction due to diet-induced obesity, are improved by chronic supplementation of GSPE. The beneficial effects caused by the administration of GSPE are exhibited as a protection against weight gain, in spite of the Cd the rats were fed. These data indicate that chronic consumption of a moderate dose of GSPE can correct an energy imbalance in a situation of diet-induced obesity, thereby improving the mitochondrial function and thermogenic capacity of the BAT.
A faithful polynomial representation of Out F3
Authors: McCool James
Published: June 2011

Let Fn be a free group of rank n and let Out Fn be its outer automorphism group. The main result of this paper is that Out F3 has a faithful representation as a group of automorphisms of the polynomial ring in seven variables over the integers. This extends a similar result for n = 2 (see Helling [3], Horowitz [5] and Rosenberger [12]), and provides a partial answer to a conjecture attributed in [5] to W. Magnus. As an application of the special nature of the representing polynomials, we obtain our second result, that Out F3 is virtually residually torsion-free nilpotent.
Proving a witness lemma in better-quasiordering theory: the method of ‘extensions’
Authors: Kříž Igor
Published: June 2011

We introduce a new method for proving ‘witness lemmas’ in BQO theory. As an application, we obtain witness-lemmas for arbitrary trees and for σ-scattered linear orderings. A positive answer to a question by Van Engelen, Miller and Steel follows.
The skein polynomial of a planar star product of two links
Authors: Murasugi Kunio , Przytycki Jozef H.
Published: June 2011

If PL(v,z) = Σbi(v)zi is the skein polynomial of a link L, and D = D1 * D2 is the diagram which is a planar star (Murasugi) product of D1 and D2 then bϕ(D)(v) = bϕ(D1)·bϕ(D2)(v) where ϕ(D) = n(D)– (s(D) – 1) and n(D) denotes the number of crossings of D, and s(D) is the number of Seifert circles of D.
A Tauberian theorem for statistical convergence
Authors: Maddox I. J.
Published: June 2011

The notion of statistical convergence of a sequence (xk) in a locally convex Hausdorff topological linear space X was introduced recently by Maddox[5], where it was shown that the slow oscillation of (sk) was a Tauberian condition for the statistical convergence of (sk).
Influence of design on the rate of convergence to normality in L1 regression
Authors: Hall Peter , Welsh A. H.
Published: June 2011

We provide a concise account of the influence of design variables on the convergence rate in an L1 regression problem. In particular, we show that the convergence rate may be characterized precisely in terms of third and fourth moments of the design variables. This result leads to necessary and sufficient conditions on the design for the Berry-Esseen rate to be achieved. We also show that a moment condition on the error distribution is necessary and sufficient for a non-uniform Berry-Esseen theorem, and that an Edgeworth expansion is possible if the design points are not too clumped.
Factors that Influence Physical Activity in Long-term Care: Perspectives of Residents, Staff, and Significant Others
Authors: Benjamin Kathleen , Edwards Nancy , Guitard Paulette , Murray Mary Ann , Caswell Wenda , Perrier Marie Josée
Published: June 2011

L’activité physique a des répercussions positives sur la santé des ainés. Toutefois, notre compréhension des facteurs qui influencent l’activité physique pour les résidents en soins de longue durée est limitée. Des résidents, des personnes significatives et des employés de neuf établissements de longue durée ont participé à des groupes de discussion (focus group). L’analyse de ces groupes de discussion révèle trois thèmes majeurs reflétant des facteurs qui semblent mitiger l’activité physique : 1) appui inadéquat pour l’activité physique; 2) routines institutionnelles omniprésentes; et 3) l’environnement physique. Tous les participants considèrent que l’activité physique est un facteur important pour préserver la santé. Des facteurs individuels, structuraux et environnementaux ont un impact sur la quantité et la qualité de l’activité physique accessible aux résidents. Ces résultats confirment le besoin de développer des stratégies pratiques et des moyens pour modifier les barrières et ancrer l’activité physique dans les soins de longue durée.
Prejudice Rivals Partisanship and Ideology When
Explaining the 2008 Presidential Vote across the
States
Authors: Highton Benjamin
Published: June 2011

This article demonstrates that racial prejudice was strongly related
to the state-level nonblack vote in the 2008 presidential election,
which featured the first African American candidate from a major
party, Barack Obama. Additional tests show that while prejudice also
explains shifts in the nonblack vote between 2004 and 2008, its
influence on voting in the 2000 and 2004 elections was modest at
best. Furthermore, there is no relationship between racial attitudes
and state-level presidential approval of George Bush in 2008. Taken
together, the findings suggest that prejudice does not have a
pervasive influence on political behavior and opinion. Instead, the
effect appears to have been triggered by the presence of Barack
Obama on the ballot. Had there been less prejudice among the
American voting public, Obama would likely have won an electoral
vote landslide.
Counting Those Who Count: The Impact of Latino Population
Growth on Redistricting in Southern States
Authors: Peralta J. Salvador , Larkin George R.
Published: June 2011

The purpose of this article is to examine the potential impact of
Hispanics on the electoral geography of the southern United States
after the 2010 decennial census. Hispanics are the largest and
fastest-growing minority group in the United States today. In
addition to traditional Hispanic destinations such as Florida and
Texas, many of the areas experiencing the most rapid growth in
Hispanic population are southern states such as Georgia, North
Carolina, and Virginia. Geographic information systems are used to
determine where majority-minority and influential districts are
likely to emerge in southern states. We argue that although the
Latino population has increased significantly over the past decade,
the proportion of Latinos living in southern states remains
relatively low in comparison to the general population. Therefore,
no new majority-minority or influence districts will emerge in
Louisiana, Mississippi, or Tennessee. Majority-minority and
influence districts are likely to emerge in Arkansas, Georgia, North
Carolina, South Carolina, and Virginia at the state and local
levels, but not at the U.S. congressional level. Texas and Florida
are the only southern states where new majority-minority and
influence districts are likely to emerge at the U.S., state, and
local levels after the 2010 decennial census.
The Modes of Theorizing in Aristotle'sPolitics
Authors: Shuster Amy L.
Published: June 2011

This article addresses the pedagogical value of teaching Aristotle'sPolitics4.1 early in an introductory course in political theory that draws texts from the history of political thought. I argue that this chapter provides an interpretive key to understanding arguments made elsewhere in thePoliticsand can be used to introduce students to the kinds of theorizing that appear in the study of politics more generally. I begin by laying out some common learning obstacles that students experience in introductory political theory courses, usingPolitics4.1 to address these issues. I then outline my approach to this text and conclude by reflecting on some of the possibilities and limitations of this method of introducing the nature of political theory to an undergraduate population.
2011 APSA Teaching and Learning Conference Track
Summaries
Authors: Hudak Kristen , Sachleben Mark , Ward Deborah E.
Published: June 2011

This track served not only to continue the discussion of the
importance of internationalizing the curriculum, but also as an
impetus for laying out a framework to do so. The papers and
subsequent discussions in this track highlighted both the challenges
and the opportunities for internationalization in the classroom and
the discipline.
“The Politics of Rights”: 107th APSA Annual
Meeting
Authors: Pewett Melissa
Published: June 2011

The APSA Annual Meeting, held September 1–4 in Seattle, Washingon, is
an opportunity to connect: with colleagues, with the political
science community, with a timely topic. Panels and roundtables allow
attendees to explore the theme “The Politics of Rights,” while
special events encourage interaction and networking. Whether you are
in search of scholarly research, an introduction to new contacts,
fresh career opportunities, or an opportunity to reconnect with
colleagues, the Annual Meeting has it all.
MORE ON THE GETTIER PROBLEM AND LEGAL PROOF:
Authors: Pardo Michael S.
Published: June 2011

In “The Gettier Problem and Legal Proof,” I argue that epistemic conditions that undermine knowledge in Gettier-type cases also potentially undermine legal verdicts. For this reason, I argue, there is a deeper connection between knowledge and legal proof than is typically presupposed or argued for in the scholarly legal literature. To support these claims, I present several examples illustrating how conditions that render epistemically justified beliefs merely accidentally true (and thus disqualify them as cases of genuine knowledge) may also render evidentially well-supported verdicts merely accidentally true for similar reasons. Such “Gettierized” verdicts, I contend, fail to realize the epistemic goal or aim of legal proof. Thus I conclude there, legal proof includes something like a knowledge requirement—in the sense that legal verdicts aim not only at truth and sufficient evidential support but also, as with knowledge, at an appropriate connection between their truth and justifying evidential support.
Dwelling and the Sacralisation of the Air: A note on acousmatic music
Authors: Dixon Martin Parker
Published: June 2011

This paper adapts Martin Heidegger's philosophy of ‘dwelling’ in order to effect a liaison between acousmatic music and ecological concern. I propose this as an alternative to both the propagandist use of music as a means of protest and to using the science of ecology as a domain that might furnish new compositional means. I advance the interpretation that acousmatic music ‘occupies the air’ in ways that transform the meaning of that dimension. It allows the sky to be sky and the earth, earth. I use the precedent of bell ringing as an example of sonic activity that occupies the air in order to further dwelling.
Advancements in Actuated Musical Instruments
Authors: Overholt Dan , Berdahl Edgar , Hamilton Robert
Published: June 2011

This article presents recent developments in actuated musical instruments created by the authors, who also describe an ecosystemic model of actuated performance activities that blur traditional boundaries between the physical and virtual elements of musical interfaces. Actuated musical instruments are physical instruments that have been endowed with virtual qualities controlled by a computer in real-time but which are neverthelesstangible. These instruments provide intuitive and engaging new forms of interaction. They are different from traditional (acoustic) and fully automated (robotic) instruments in that they produce sound via vibrating element(s) that are co-manipulated by humans and electromechanical systems. We examine the possibilities that arise when such instruments are played in different performative environments and music-making scenarios, and we postulate that such designs may give rise to new methods of musical performance. The Haptic Drum, the Feedback Resonance Guitar, the Electromagnetically Prepared Piano, the Overtone Fiddle and Teleoperation with Robothands are described, along with musical examples and reflections on the emergent properties of the performance ecologies that these instruments enable. We look at some of the conceptual and perceptual issues introduced by actuated musical instruments, and finally we propose some directions in which such research may be headed in the future.
Wissensorganisation in teilautonomen Arbeitsgruppen
Authors: Henschel Angela , Kauffeld Simone , Neininger Alexandra
Published: June 2011

Die vorliegende Untersuchung geht der Fragestellung nach, welche Bedeutung geteiltes und ungeteiltes Objektwissen für die Produktivität, Ideengenerierung und -umsetzung sowie das Team Commitment in teilautonomen Arbeitsgruppen hat. Es wurden 42 teilautonome Arbeitsgruppen zu drei Messzeitpunkten untersucht. Die Datenerhebung umfasste Selbsteinschätzungen, Beobachtungsdaten und objektive Kennzahlen. Die Ergebnisse zeigen, dass teilautonome Arbeitsgruppen von geteiltem Objektwissen hinsichtlich der Produktivität profitieren. Für das Team Commitment hingegen erweist sich das ungeteilte Objektwissen als positiv. Geteiltes und ungeteiltes Objektwissen scheinen für das Generieren und Umsetzen von Ideen keine Bedeutung zu haben. Praktische Implikationen werden diskutiert.
The role of extension during brittle deformation within the NW Indian Himalaya
Authors: Hintersberger E. , Thiede R. C. , Strecker M. R.
Published: June 2011

Synorogenic extension has been recognized as an integral structural constituent of mountain belts and high‐elevation plateaus during their evolution. In the Himalaya, both orogen‐parallel and orogen‐normal extension has been recognized. However, the underlying driving forces for extension and their timing are still a matter of debate. Here we present new fault kinematic data based on systematic measurements of hundreds of outcrop‐scale brittle fault planes in the NW Indian Himalaya. This new data set, as well as field observations including crosscutting relationships, mineral fibers on fault planes, and correlations with deformation structures in lake sediments, allows us to distinguish different deformation styles. The overall strain pattern derived from our data reflects the large regional contractional deformation pattern very well but also reveals significant extensional deformation in a region, which is dominated by shortening. In total, we were able to identify six deformation styles, most of which are temporally and spatially linked, representing protracted shortening. Our observations also furnish the basis for a detailed overview of the younger deformation history in the NW Himalaya, which has been characterized by extension overprinting previously generated structures related to shortening. The four dominant deformation styles are (1) shortening parallel to the regional convergence direction; (2) arc‐normal extension; (3) arc‐parallel extension; and finally, (4) E–W extension. This is the first data set where a succession of both arc‐normal and E–W extension has been documented in the Himalaya. Importantly, our observations help differentiate E–W extension triggered by processes within the Tibetan Plateau from arc‐parallel and arc‐normal extension originating from the curvature of the Himalayan orogen.
Aboveground‐belowground linkages: Biotic interactions, ecosystem processes, and global change
Authors: Anderson Laurel J.
Published: June 2011

The discovery of unexpected connections among organisms that seemingly have nothing to do with one another is one of the most exciting aspects of ecological science. Aboveground‐Belowground Linkages: Biotic Interactions, Ecosystem Processes, and Global Change, by Richard Bardgett and David Wardle, reminds readers that interactions among soil microbes, plants, herbivores, predators, and the physical environment represent some of the most fascinating of these discoveries and that much remains to be revealed. Indeed, given the known influences of soils on plant productivity and the global carbon and nitrogen cycles, understanding the mechanisms that link aboveground and belowground processes is critical for accurate assessments of how climate change may affect ecosystem goods and services that support humans. Bardgett and Wardle make the need for further work in this area abundantly clear as they synthesize the current state of knowledge on aboveground and belowground interactions using diverse and interesting examples drawn from an extensive review of the literature.
Controls of lithospheric structure and plate kinematics on rift architecture and evolution: An experimental modeling of the Baikal rift
Authors: Corti Giacomo , Calignano Elisa , Petit Carole , Sani Federico
Published: June 2011

Analog models investigate the evolution and architecture of the Baikal rift in relation to the rheology of the extending lithosphere and rift kinematics. The models focus on the development of the narrow, deep, and asymmetric basins composing Lake Baikal and reproduce the extension between the strong Siberian craton and the weaker Sayan‐Baikal belt. Model results suggest that the presence of a near‐vertical weak suture separating the cratonic keel from the mobile belt represents the more convenient rheological configuration leading to a narrow rift characterized by prominent vertical motions and deep depressions. These depressions are typically asymmetric, and model results suggest that this asymmetry is a consequence of lateral variations in lithospheric rheology, which is in turn related to both the variation in thickness of the strong mantle and, more importantly, the variation in the brittle‐ductile transition depth between the craton and the belt. A significant shallowing of the brittle‐ductile transition in the crust passing from the craton to the belt is required to fit the asymmetric architecture of the Baikal basins, with a master fault on the craton side and a monocline with no significant faulting on the belt side. Analysis of the model deformation pattern suggests that the overall architecture of the basins hosting Lake Baikal is best fitted for a N140°E directed extension, similar to the current GPS‐derived motion and compatible with the stress field inferred on the basis of fault and focal mechanism data. This kinematics (along with the shape of the Siberian craton) exerted the major control on the plan view fault architecture and its along‐axis variations.
Ultraviolet electroluminescence from two-dimensional ZnO nanomesh/GaN heterojunction light emitting diodes
Authors: Ye Jing , Zhao Yu , Tang Libin , Chen Li-Miao , Luk C. M. , Yu S. F. , Lee S. T. , Lau S. P.
Published: June 2011

The authors report the fabrication of heterojunction light emitting diodes (LEDs) based on two-dimensional (2D) hexagonal ordered n-type ZnO nanomesh and p-type GaN. The 2D ZnO nanomesh array was prepared by employing polystyrene spheres as a template. When a forward bias was applied to the LED, a strong ultraviolet (UV) electroluminescence peaked at 385 nm can be observed. The peak deconvolution revealed three emission peaks at 370, 388, and 420 nm. The origin of these emission peaks will be discussed. In addition, the LED was capable of exciting a red phosphor to convert UV light into red light.
Development of interdigital transducer sensors for non-destructive characterization of thin films using high frequency Rayleigh waves
Authors: Deboucq Julien , Duquennoy Marc , Ouaftouh Mohammadi , Jenot Frédéric , Carlier Julien , Ourak Mohamed
Published: June 2011

In this paper, Rayleigh waves were generated and studied over a broad frequency range (5–50 MHz) and from the dispersion phenomenon, two substrate on layer type-samples with thin layer thicknesses of 1 μm and 500 nm, respectively, were characterized. The originality in this paper is the use of surface acoustic wave interdigital transducers (IDT) to generate surface waves as well as the development of a measuring device enabling an accurate estimation of the phase velocity to be obtained, which is essential in order to characterize such thin layers. Considering the excitation frequencies (5–50 MHz) and therefore the widths necessary on the electrodes for these types of IDT sensors (20–200 μm), a lift-off procedure was chosen to deposit the electrodes on the lithium niobate (LiNbO3) piezoelectric substrates. The use of these IDT, first enabled problems of loss and attenuation linked to the high frequency of conventional sensors (wedge sensors) to be overcome and second to carry out quasi-monochromatic measurements in order to obtain an extremely accurate estimation of the phase velocity with rapid post-processing. An inverse method provided a very precise estimation of the thickness of the layers and the elastic constants of the substrate. The estimations of the thicknesses were then confirmed by measurements with a profilometer.
Computer investigations on the asymptotic behavior of the rate coefficient for the annihilation reaction A + A → product and the trapping reaction in three dimensions
Authors: Litniewski Marek , Gorecki Jerzy
Published: June 2011

We have performed intensive computer simulations of the irreversible annihilation reaction: A + A → C + C and of the trapping reaction: A + B → C + B for a variety of three-dimensional fluids composed of identical spherical particles. We have found a significant difference in the asymptotic behavior of the rate coefficients for these reactions. Both the rate coefficients converge to the same value with time t going to infinity but the convergence rate is different: the O(t−1/2) term for the annihilation reaction is higher than the corresponding term for the trapping reaction. The simulation results suggest that ratio of the terms is a universal quantity with the value equal to 2 or slightly above. A model for the annihilation reaction based on the superposition approximation predicts the difference in the O(t−1/2) terms, but overestimates the value for the annihilation reaction by about 30%. We have also performed simulations for the dimerization process: A + A → E, where E stands for a dimer. The dimerization decreases the reaction rate due to the decrease in the diffusion constant for A. The effect is successfully predicted by a simple model.
Hafnium dioxide as a passivating layer and diffusive barrier in ZnO/Ag Schottky junctions obtained by atomic layer deposition
Authors: Krajewski Tomasz A. , Luka Grzegorz , Gieraltowska Sylwia , Zakrzewski Adam J. , Smertenko Petro S. , Kruszewski Piotr , Wachnicki Lukasz , Witkowski Bartlomiej S. , Lusakowska Elzbieta , Jakiela Rafal , Godlewski Marek , Guziewicz Elzbieta
Published: June 2011

This paper reports on ZnO/Ag Schottky junctions obtained by the low temperature atomic layer deposition process. Introducing the thin (from 1.25 to 7.5 nm) layer of hafnium dioxide between the ZnO layer and evaporated Ag Schottky contact improves the rectification ratio to about 105 at 2V. For the ZnO/Ag junctions without the HfO2 interlayer, the rectification ratio is only 102. We assign this effect to the passivation of ZnO surface accumulation layer that is reported for ZnO thin films.
Two Wrongs Don't Make a Right: State and Private Organic Certification in New Zealand Dairy
Authors: Schewe Rebecca L
Published: June 2011

The global agrifood system is governed by a wide array of organic labels, certifications, and standards. Many of these labels are private, third-party certifications rather than strictly governmental standards; even many national organic standards such as the United States Department of Agriculture National Organic Program (USDA NOP) are actually a hybridization of state-led and private regulatory schemes. Both state-led and private agricultural regulations raise concerns over their relevance to local environments, consistent and transparent application, and extent of democratic stakeholder involvement. This study compares two organic regulations—the USDA NOP and Demeter International—in New Zealand's dairy industry on these key issues of relevance, consistency, transparency, and democracy. I find that the hybrid state/private regulation of the USDA NOP has replicated weaknesses of both state and private regulatory models: the monolithic and hegemonic nature of state regulation has combined with the lack of consistency, transparency, and democracy of private regulation. By comparison, Demeter International certification uses an international equivalency program to increase democratic stakeholder involvement from farmers and relevance to local environments, but has not fully addressed concerns of consistency and transparency associated with private regulations. By focusing on both the structural aspects of neoliberal regulations and farmers' and processors' lived experience of these disparate regulations, this research expands existing theories of neoliberalization to address the diversity of regulation.
Community BIAs as Practices of Assemblage: Contingent Politics in the Neoliberal City
Authors: Rankin Katharine N , Delaney Jim
Published: June 2011

Business Improvement Areas (BIAs) are a domain of urban governance that has been aptly characterized as a form of neoliberal urbanization aimed at improving the business climate of downtowns. This paper engages with a growing body of literature on contingent neoliberal urbanisms to consider BIAs as an assemblage of coevolving projects and actors. It focuses specifically on two ‘community’ BIAs in Toronto's downtown West, where recent actions of differently positioned stakeholders effectively reveal how multiple agendas can inform BIA practices. Our objective is twofold: (a) to draw attention to the practices of smaller, community-based BIAs that predominate in North America; and (b) to explore the analytical and political openings that arise when institutions commonly identified as neoliberal are investigated as an assemblage of related but distinctive and sometimes disjunctive projects.
The Geographies of Mixed-Ethnicity Families
Authors: Smith Darren P , Edwards Rosalind , Caballero Chamion
Published: June 2011

This paper examines the underresearched residential geographies of mixed-ethnicity families. Analyses of 2001 Great Britain Census data reveal uneven patterns, with different concentrations of mixed-ethnicity families in distinct locations. The findings suggest that distributions of mixed-ethnicity families are not aligned with respective minority ethnic groups. The concentration of mixed-ethnicity families within ethnically diverse neighbourhoods is, in part, substantiated. The discussion disrupts media representations of mixed ethnicity and assumptions of the marginalisation of deprived, mixed-ethnicity families, making a contribution to theoretical debates of processes of sociospatial segregation, ethnicity, and neighbourhood change.
Altered temporal patterns of anxiety in aged and amyloid precursor protein (APP) transgenic mice
Authors: Bedrosian Tracy A. , Herring Kamillya L. , Weil Zachary M. , Nelson Randy J.
Published: June 2011

Both normal aging and dementia are associated with dysregulation of the biological clock, which contributes to disrupted circadian organization of physiology and behavior. Diminished circadian organization in conjunction with the loss of cholinergic input to the cortex likely contributes to impaired cognition and behavior. One especially notable and relatively common circadian disturbance among the aged is “sundowning syndrome,” which is characterized by exacerbated anxiety, agitation, locomotor activity, and delirium during the hours before bedtime. Sundowning has been reported in both dementia patients and cognitively intact elderly individuals living in institutions; however, little is known about temporal patterns in anxiety and agitation, and the neurobiological basis of these rhythms remains unspecified. In the present study, we explored the diurnal pattern of anxiety-like behavior in aged and amyloid precursor protein (APP) transgenic mice. We then attempted to treat the observed behavioral disturbances in the aged mice using chronic nightly melatonin treatment. Finally, we tested the hypothesis that time-of-day differences in acetylcholinesterase and choline acetyltransferase expression and general neuronal activation (i.e., c-Fos expression) coincide with the behavioral symptoms. Our results show a temporal pattern of anxiety-like behavior that emerges in elderly mice. This behavioral pattern coincides with elevated locomotor activity relative to adult mice near the end of the dark phase, and with time-dependent changes in basal forebrain acetylcholinesterase expression. Transgenic APP mice show a similar behavioral phenomenon that is not observed among age-matched wild-type mice. These results may have useful applications to the study and treatment of age- and dementia-related circadian behavioral disturbances, namely, sundowning syndrome.
Artemisinin activity againstPlasmodium falciparumrequires hemoglobin uptake and digestion
Authors: Klonis Nectarios , Crespo-Ortiz Maria P. , Bottova Iveta , Abu-Bakar Nurhidanatasha , Kenny Shannon , Rosenthal Philip J. , Tilley Leann
Published: June 2011

Combination regimens that include artemisinin derivatives are recommended as first line antimalarials in most countries where malaria is endemic. However, the mechanism of action of artemisinin is not fully understood and the usefulness of this drug class is threatened by reports of decreased parasite sensitivity. We treatedPlasmodium falciparumfor periods of a few hours to mimic clinical exposure to the short half-life artemisinins. We found that drug treatment retards parasite growth and inhibits uptake of hemoglobin, even at sublethal concentrations. We show that potent artemisinin activity is dependent on hemoglobin digestion by the parasite. Inhibition of hemoglobinase activity with cysteine protease inhibitors, knockout of the cysteine protease falcipain-2 by gene deletion, or direct deprivation of host cell lysate, significantly decreases artemisinin sensitivity. Hemoglobin digestion is also required for artemisinin-induced exacerbation of oxidative stress in the parasite cytoplasm. Arrest of hemoglobin digestion by early stage parasites provides a mechanism for surviving short-term artemisinin exposure. These insights will help in the design of new drugs and new treatment strategies to circumvent drug resistance.
Raft domains of variable properties and compositions in plasma membrane vesicles
Authors: Levental Ilya , Grzybek Michal , Simons Kai
Published: June 2011

Biological membranes are compartmentalized for functional diversity by a variety of specific protein–protein, protein–lipid, and lipid–lipid interactions. A subset of these are the preferential interactions between sterols, sphingolipids, and saturated aliphatic lipid tails responsible for liquid–liquid domain coexistence in eukaryotic membranes, which give rise to dynamic, nanoscopic assemblies whose coalescence is regulated by specific biochemical cues. Microscopic phase separation recently observed in isolated plasma membranes (giant plasma membrane vesicles and plasma membrane spheres) (
i
) confirms the capacity of compositionally complex membranes to phase separate, (
ii
) reflects the nanoscopic organization of live cell membranes, and (
iii
) provides a versatile platform for the investigation of the compositions and properties of the phases. Here, we show that the properties of coexisting phases in giant plasma membrane vesicles are dependent on isolation conditions—namely, the chemicals used to induce membrane blebbing. We observe strong correlations between the relative compositions and orders of the coexisting phases, and their resulting miscibility. Chemically unperturbed plasma membranes reflect these properties and validate the observations in chemically induced vesicles. Most importantly, we observe domains with a continuum of varying stabilities, orders, and compositions induced by relatively small differences in isolation conditions. These results show that, based on the principle of preferential association of raft lipids, domains of various properties can be produced in a membrane environment whose complexity is reflective of biological membranes.
Sialylation and fucosylation of epidermal growth factor receptor suppress its dimerization and activation in lung cancer cells
Authors: Liu Ying-Chih , Yen Hsin-Yung , Chen Chien-Yu , Chen Chein-Hung , Cheng Ping-Fu , Juan Yi-Hsiu , Chen Chung-Hsuan , Khoo Kay-Hooi , Yu Chong-Jen , Yang Pan-Chyr , Hsu Tsui-Ling , Wong Chi-Huey
Published: June 2011

Protein glycosylation is an important posttranslational process, which regulates protein folding and functional expression. Studies have shown that abnormal glycosylation in tumor cells affects cancer progression and malignancy. In the current study, we have identified sialylated proteins using an alkynyl sugar probe in two different lung cancer cell lines, CL1-0 and CL1-5 with distinct invasiveness derived from the same parental cell line. Among the identified sialylated proteins, epidermal growth factor receptor (EGFR) was chosen to understand the effect of sialylation on its function. We have determined the differences in glycan sequences of EGFR in both cells and observed higher sialylation and fucosylation of EGFR in CL1-5 than in CL1-0. Further study suggested that overexpression of sialyltransferases in CL1-5 and α1,3-fucosyltransferases (FUT4 or FUT6) in CL1-5 and A549 cells would suppress EGFR dimerization and phosphorylation upon EGF treatment, as compared to the control and CL1-0 cells. Such modulating effects on EGFR dimerization were further confirmed by sialidase or fucosidase treatment. Thus, increasing sialylation and fucosylation could attenuate EGFR-mediated invasion of lung cancer cells. However, incorporation of the core fucose by α1,6-fucosylatransferase (FUT8) would promote EGFR dimerization and phosphorylation.
Entropy and the driving force for the filling of carbon nanotubes with water
Authors: Pascal Tod A. , Goddard William A. , Jung Yousung
Published: June 2011

The spontaneous filling of hydrophobic carbon nanotubes (CNTs) by water observed both experimentally and from simulations is counterintuitive because confinement is generally expected to decrease both entropy and bonding, and remains largely unexplained. Here we report the entropy, enthalpy, and free energy extracted from molecular dynamics simulations of water confined in CNTs from 0.8 to 2.7-nm diameters. We find for all sizes that water inside the CNTs is more stable than in the bulk, but the nature of the favorable confinement of water changes dramatically with CNT diameter. Thus we find (
i
) an entropy (both rotational and translational) stabilized, vapor-like phase of water for small CNTs (0.8–1.0 nm), (
ii
) an enthalpy stabilized, ice-like phase for medium-sized CNTs (1.1–1.2 nm), and (
iii
) a bulk-like liquid phase for tubes larger than 1.4 nm, stabilized by the increased translational entropy as the waters sample a larger configurational space. Simulations with structureless coarse-grained water models further reveal that the observed free energies and sequence of transitions arise from the tetrahedral structure of liquid water. These results offer a broad theoretical basis for understanding water transport through CNTs and other nanostructures important in nanofluidics, nanofiltrations, and desalination.
Resting-state activity in development and maintenance of normal brain function
Authors: Pizoli Carolyn E. , Shah Manish N. , Snyder Abraham Z. , Shimony Joshua S. , Limbrick David D. , Raichle Marcus E. , Schlaggar Bradley L. , Smyth Matthew D.
Published: June 2011

One of the most intriguing recent discoveries concerning brain function is that intrinsic neuronal activity manifests as spontaneous fluctuations of the blood oxygen level–dependent (BOLD) functional MRI signal. These BOLD fluctuations exhibit temporal synchrony within widely distributed brain regions known as resting-state networks. Resting-state networks are present in the waking state, during sleep, and under general anesthesia, suggesting that spontaneous neuronal activity plays a fundamental role in brain function. Despite its ubiquitous presence, the physiological role of correlated, spontaneous neuronal activity remains poorly understood. One hypothesis is that this activity is critical for the development of synaptic connections and maintenance of synaptic homeostasis. We had a unique opportunity to test this hypothesis in a 5-y-old boy with severe epileptic encephalopathy. The child developed marked neurologic dysfunction in association with a seizure disorder, resulting in a 1-y period of behavioral regression and progressive loss of developmental milestones. His EEG showed a markedly abnormal pattern of high-amplitude, disorganized slow activity with frequent generalized and multifocal epileptiform discharges. Resting-state functional connectivity MRI showed reduced BOLD fluctuations and a pervasive lack of normal connectivity. The child underwent successful corpus callosotomy surgery for treatment of drop seizures. Postoperatively, the patient's behavior returned to baseline, and he resumed development of new skills. The waking EEG revealed a normal background, and functional connectivity MRI demonstrated restoration of functional connectivity architecture. These results provide evidence that intrinsic, coherent neuronal signaling may be essential to the development and maintenance of the brain's functional organization.
Phosphoinositide 3-kinase signaling pathway mediated by p110α regulates invadopodia formation
Authors: Yamaguchi Hideki , Yoshida Shuhei , Muroi Emi , Yoshida Nachi , Kawamura Masahiro , Kouchi Zen , Nakamura Yoshikazu , Sakai Ryuichi , Fukami Kiyoko
Published: June 2011

Invadopodia are extracellular matrix–degrading protrusions formed by invasive cancer cells that are thought to function in cancer invasion. Although many invadopodia components have been identified, signaling pathways that link extracellular stimuli to invadopodia formation remain largely unknown. We investigate the role of phosphoinositide 3-kinase (PI3K) signaling during invadopodia formation. We find that in human breast cancer cells, both invadopodia formation and degradation of a gelatin matrix were blocked by treatment with PI3K inhibitors or sequestration of D-3 phosphoinositides. Functional analyses revealed that among the PI3K family proteins, the class I PI3K catalytic subunit p110α, a frequently mutated gene product in human cancers, was selectively involved in invadopodia formation. The expression of p110α with cancerous mutations promoted invadopodia-mediated invasive activity. Furthermore, knockdown or inhibition of PDK1 and Akt, downstream effectors of PI3K signaling, suppressed invadopodia formation induced by p110α mutants. These data suggest that PI3K signaling via p110α regulates invadopodia-mediated invasion of breast cancer cells.