bluuebunny/crossref_metadata_2025 huggingface dataset:
Dry etching characteristics of TaN absorber for extreme ultraviolet mask with Ru buffer layer
Authors: Park Wanjae , Kwon Ohyung , Whang Ki-Woong , Lee Jeongyun
Published: May 2012

The extreme ultraviolet (EUV) mask using reflective optics has a structure totally different from that of the conventional mask. This study investigated the dry etching characteristics of the EUV mask layer in which TaN and Ru were used as the absorber and buffer layer, respectively. The TaN absorber etching requires high etch selectivity of TaN over Ru to achieve the high EUV reflectivity. In this work, the TaN etching rate was investigated with various halogen gases in the capacitively coupled plasma type etching system. The etching rates with the fluorinated gases were higher than that with the chlorinated gas. Ru could not be etched without oxygen in all of the considered etch gases. The etching rate of TaN and its etch selectivity to Ru were increased with the increase of RF power, pressure and SF6 gas flow ratio. When the real EUV mask specimens were 100% over etched under the highest selectivity etching condition, the Ru buffer layer still remained, which was confirmed by x-ray photoelectron spectroscopy analysis. The surface roughness of etched reflective mirror was very small, and the EUV reflectivity was equivalent to that of the reference mirror (EUV reflectivity is over 60%) which was confirmed by measuring the intensity and the diffracted pattern of 13.5 nm EUV obtained using x-ray charge coupled device camera. The Ru buffer layer could be removed by the O2 plasma used in the posterior photo resist ashing process without affecting the EUV reflectivity.
PShield: An exact three‐dimensional numerical solution for determining optimal shielding designs for PET/CT facilities
Authors: Pasciak Alexander S. , Jones A. Kyle
Published: May 2012

Purpose:

Calculation of radiation shielding requirements for high‐workload positron emission tomography/computed tomography (PET/CT) installations using the methods proposed by Task Group 108 (TG 108) of the American Association of Physicists in Medicine can be a complex task. The principal challenge that makes PET shielding design more complex than other diagnostic imaging modalities, aside from the higher photon energy, is that it is a multisource problem for which no unique solution exists. Although many solutions may meet shielding design dose limits, each solution has a different cost for materials and construction according to the type, thickness, weight, and location of the specified shielding. Here, the authors describe PShield, an algorithm that incorporates three‐dimensional (3D) numerical methods to optimize PET shielding and delivers a cost‐optimized solution while making no approximations.

Methods:

The PShield algorithm uses a sequential quadratic programming routine to optimize PET shielding by minimizing a cost function in three‐dimensions using extrapolations of the formulas published by TG 108. PShield makes no approximations and accounts for the contribution of every radiation source to the dose rate at every location in the problem using a discrete mesh. The authors used two simple examples of shielding problems to compare PShield with the TG 108 methods.

Results:

The benefit of applying an optimization routine to an indeterminate problem is the identification of the only solution to the problem that minimizes the desired cost function. Choosing a poorly optimized solution can result in a shielding design that requires more shielding than an optimized design to reach the same dose rate at a given control point. The increased accuracy afforded by PShield ensures that dose rates at every point in a control area never exceed the design dose, whereas approximations often used to evaluate TG 108 methods may result in hot spots where the dose rate exceeds the design dose.

Conclusions:

The PShield algorithm is an exact 3D numerical solution for optimal PET/CT shielding based on the methods proposed by TG 108. Selection of the optimum shielding design can minimize the total material cost and structural burden of installed shielding or achieve other goals desired by a specific site. This is especially important for modern PET/CT suites, where increases in scanner capabilities have resulted in more complex shielding problems and the potential for high occupational doses.
Influence of robust optimization in intensity‐modulated proton therapy with different dose delivery techniques
Authors: Liu Wei , Li Yupeng , Li Xiaoqiang , Cao Wenhua , Zhang Xiaodong
Published: May 2012

Purpose:

The distal edge tracking (DET) technique in intensity‐modulated proton therapy (IMPT) allows for high energy efficiency, fast and simple delivery, and simple inverse treatment planning; however, it is highly sensitive to uncertainties. In this study, the authors explored the application of DET in IMPT (IMPT‐DET) and conducted robust optimization of IMPT‐DET to see if the planning technique's sensitivity to uncertainties was reduced. They also compared conventional and robust optimization of IMPT‐DET with three‐dimensional IMPT (IMPT‐3D) to gain understanding about how plan robustness is achieved.

Methods:

They compared the robustness of IMPT‐DET and IMPT‐3D plans to uncertainties by analyzing plans created for a typical prostate cancer case and a base of skull (BOS) cancer case (using data for patients who had undergone proton therapy at our institution). Spots with the highest and second highest energy layers were chosen so that the Bragg peak would be at the distal edge of the targets in IMPT‐DET using 36 equally spaced angle beams; in IMPT‐3D, 3 beams with angles chosen by a beam angle optimization algorithm were planned. Dose contributions for a number of range and setup uncertainties were calculated, and a worst‐case robust optimization was performed. A robust quantification technique was used to evaluate the plans' sensitivity to uncertainties.

Results:

With no uncertainties considered, the DET is less robust to uncertainties than is the 3D method but offers better normal tissue protection. With robust optimization to account for range and setup uncertainties, robust optimization can improve the robustness of IMPT plans to uncertainties; however, our findings show the extent of improvement varies.

Conclusions:

IMPT's sensitivity to uncertainties can be improved by using robust optimization. They found two possible mechanisms that made improvements possible: (1) a localized single‐field uniform dose distribution (LSFUD) mechanism, in which the optimization algorithm attempts to produce a single‐field uniform dose distribution while minimizing the patching field as much as possible; and (2) perturbed dose distribution, which follows the change in anatomical geometry. Multiple‐instance optimization has more knowledge of the influence matrices; this greater knowledge improves IMPT plans' ability to retain robustness despite the presence of uncertainties.
Vitamin K
2
Is a Mitochondrial Electron Carrier That Rescues Pink1 Deficiency
Authors: Vos Melissa , Esposito Giovanni , Edirisinghe Janaka N. , Vilain Sven , Haddad Dominik M. , Slabbaert Jan R. , Van Meensel Stefanie , Schaap Onno , De Strooper Bart , Meganathan R. , Morais Vanessa A. , Verstreken Patrik
Published: May 2012

Keeping Mitochondria in the Pink

Pink1 is a mitochondrial kinase, and loss of Pink1 function in flies and mice results in the accumulation of inefficient mitochondria. In a screen for modifiers of the Parkinson-associated gene,
pink1
,

Vos
et al.

(p.
1306
, published online 10 May; see the Perspective by

Bhalerao and Clandinin

) identified the fruit fly homolog of UBIAD1, “Heix.” UBIAD1 was localized in mitochondria and was able to convert vitamin K
1
into vitamin K
2
/menaquinone (MK-
n, n
the number of prenylgroups). In bacteria, vitamin K
2
/MK-
n
acts as an electron carrier in the membrane and, similarly, in
Drosophila
, mitochondrial vitamin K
2
appeared to act as an electron carrier to facilitate adenosine triphosphate production. Fruit flies that lack
heix
showed severe mitochondrial defects that could be rescued by administering vitamin K
2
.
A Rogue Earthquake Off Sumatra
Authors: McGuire Jeffrey J. , Beroza Gregory C.
Published: May 2012

A magnitude 8.6 strike-slip earthquake within an oceanic plate raises fundamental questions about earthquake physics.
Genome Sequence of Shigella flexneri Serotype 5a Strain M90T Sm
Authors: Onodera Naoko T. , Ryu Julie , Durbic Tanja , Nislow Corey , Archibald John M. , Rohde John R.
Published: May 2012

Bacteria of the genus
Shigella
are a major cause of death worldwide (L. von Seidlein et al., PLoS Med. 3:e353, 2006). We sequenced the genome of
Shigella flexneri
strain M90T Sm (serotype 5a) and compared it to the published genome sequence of
S. flexneri
strain 8401 (serotype 5b).
Draft Genome of a Brazilian Avian-Pathogenic Escherichia coli Strain and
In Silico
Characterization of Virulence-Related Genes
Authors: Rojas Thaís Cabrera Galvão , Parizzi Lucas Pedersen , Tiba Monique Ribeiro , Chen Lihong , Pereira Gonçalo Amarante Guimarães , Sangal Vartul , Yang Jian , Yu Jun , Dias da Silveira Wanderley
Published: May 2012

Avian-pathogenic
Escherichia coli
(APEC) strains cause extraintestinal diseases in avian species. Here, we present the draft genome of an APEC strain (SCI-07) from Brazil that was isolated from skin lesions (gelatinous edema) on the head and periorbital tissues of a laying hen with swollen head syndrome.
Genome Sequence of Sphingomonas sp. Strain PAMC 26621, an Arctic-Lichen-Associated Bacterium Isolated from a Cetraria sp
Authors: Lee Hyoungseok , Shin Seung Chul , Lee Jungeun , Kim Su Jin , Kim Bum-Keun , Hong Soon Gyu , Kim Eun Hye , Park Hyun
Published: May 2012

The lichen-associated bacterial strain
Sphingomonas
sp. PAMC 26621 was isolated from an Arctic lichen
Cetraria
sp. on Svalbard Islands. Here we report the draft genome sequence of this strain, which could provide novel insights into the molecular principles of lichen-microbe interactions.
Draft Genome Sequences of the Diarrheagenic Escherichia coli Collection
Authors: Hazen Tracy H. , Sahl Jason W. , Redman Julia C. , Morris Carolyn R. , Daugherty Sean C. , Chibucos Marcus C. , Sengamalay Naomi A. , Fraser-Liggett Claire M. , Steinsland Hans , Whittam Thomas S. , Whittam Beth , Manning Shannon D. , Rasko David A.
Published: May 2012

We report the draft genome sequences of the collection referred to as the
Escherichia coli
DECA collection, which was assembled to contain representative isolates of the 15 most common diarrheagenic clones in humans (
http://shigatox.net/new/
). These genomes represent a valuable resource to the community of researchers who examine these enteric pathogens.
An evaluation of the effectiveness and cost effectiveness of the National Exercise Referral Scheme in Wales, UK: a randomised controlled trial of a public health policy initiative
Authors: Murphy Simon Mark , Edwards Rhiannon Tudor , Williams Nefyn , Raisanen Larry , Moore Graham , Linck Pat , Hounsome Natalia , Din Nafees Ud , Moore Laurence
Published: May 2012

Background

The Wales National Exercise Referral Scheme (NERS) is a 16-week programme including motivational interviewing, goal setting and relapse prevention.

Method

A pragmatic randomised controlled trial with nested economic evaluation of 2160 inactive participants with coronary heart disease risk (CHD, 1559, 72%), mild to moderate depression, anxiety or stress (79, 4%) or both (522, 24%) randomised to receive (1) NERS or (2) normal care and brief written information. Outcome measures at 12 months included the 7-day physical activity recall, the hospital anxiety and depression scale.

Results

Ordinal regression identified increased physical activity among those randomised to NERS compared with those receiving normal care in all participants (OR 1.19, 95% CI 0.99 to 1.43), and among those referred for CHD only (OR 1.29, 95% CI 1.04 to 1.60). For those referred for mental health reason alone, or in combination with CHD, there were significantly lower levels of anxiety (OR −1.56, 95% CI −2.75 to −0.38) and depression (OR −1.39, 95% CI −2.60 to −0.18), but no effect on physical activity. The base-case incremental cost-effectiveness ratio was £12 111 per quality adjusted life year, falling to £9741 if participants were to contribute £2 per session.

Conclusions

NERS was effective in increasing physical activity among those referred for CHD risk only. Among mental health referrals, NERS did not influence physical activity but was associated with reduced anxiety and depression. Effects were dependent on adherence. NERS is likely to be cost effective with respect to prevailing payer thresholds.

Trial registration

Current Controlled TrialsISRCTN47680448.
ON BEGINS, MEETS AND BEFORE
Authors: BRESOLIN DAVIDE , SALA PIETRO , SCIAVICCO GUIDO
Published: May 2012

Interval temporal logics (ITLs) are logics for reasoning about temporal statements expressed over intervals, i.e., periods of time. The most famous temporal logic for intervals studied so far is probably Halpern and Shoham's HS, which is the logic of the thirteen Allen's interval relations. Unfortunately, HS and most of its fragments are undecidable. This discouraged the research in this area until recently, when a number non-trivial decidable ITLs have been discovered. This paper is a contribution towards the complete classification of all different fragments of HS. We consider here different combinations of the interval relations begins (B), meets (A), later (L) and their inverses [Formula: see text], [Formula: see text] and [Formula: see text]. We know from previous work that the combination [Formula: see text] is decidable only when finite domains are considered (and undecidable elsewhere), and that [Formula: see text] is decidable over the natural numbers. In the present paper we show that, over strongly discrete linear models (e.g. finite orders, the naturals, the integers), decidability of [Formula: see text] can be further extended to capture the language [Formula: see text], which lies strictly in between [Formula: see text] and [Formula: see text]. The logic [Formula: see text] turns out to be maximal w.r.t decidability over the considered classes, and its satisfiability problem is EXPSPACE-complete. In this paper we also provide an optimal non-deterministic decision procedure, and we show that the language is powerful enough to polynomially encode metric constraints on the length of the current interval.
BLACKWELL OPTIMAL STRATEGIES IN PRIORITY MEAN-PAYOFF GAMES
Authors: GIMBERT HUGO , ZIELONKA WIESŁAW
Published: May 2012

We examine perfect information stochastic mean-payoff games – a class of games containing as special sub-classes the usual mean-payoff games and parity games. We show that deterministic memoryless strategies that are optimal for discounted games with state-dependent discount factors close to 1 are optimal for priority mean-payoff games establishing a strong link between these two classes.
ON THE COMPUTATIONAL CAPACITY OF PARALLEL COMMUNICATING FINITE AUTOMATA
Authors: BORDIHN HENNING , KUTRIB MARTIN , MALCHER ANDREAS
Published: May 2012

Systems of parallel finite automata communicating by states are investigated. We consider deterministic and nondeterministic devices and distinguish four working modes. It is known that systems in the most general mode are as powerful as one-way multi-head finite automata. Here we solve some open problems on the computational capacity of systems working in the remaining modes. In particular, it is shown that deterministic returning and non-returning devices are equivalent, and that there are languages which are accepted by deterministic returning and centralized systems but cannot be accepted by deterministic non-returning centralized systems. Furthermore, we show that nondeterministic systems are strictly more powerful than their deterministic variants in all the four working modes. Finally, incomparability with the classes of (deterministic) (linear) context-free languages as well as the Church-Rosser languages is derived.
NEW CONSTRUCTIONS OF VECTORIAL BOOLEAN FUNCTIONS WITH GOOD CRYPTOGRAPHIC PROPERTIES
Authors: DONG DESHUAI , QU LONGJIANG , FU SHAOJING , LI CHAO
Published: May 2012

Vectorial Boolean functions play an important role in cryptography. How to construct vectorial Boolean functions with good cryptographic properties is a nice problem that worth to be investigated. In this paper we present several constructions of balanced vectorial Boolean functions with high algebraic immunity, high(or optimum) algebraic degree, and very high nonlinearity. In some cases, the constructed functions also achieve optimum algebraic immunity.
COSMOLOGICAL CONSTANT, GENERATION OF DIMENSIONS AND THE EFFECTS OF ANISOTROPY IN MULTIDIMENSIONAL SPACETIME
Authors: YAKOVLEV SERGEY V.
Published: May 2012

In the paper, multidimensional anisotropic metric and density of vacuum energy in the Kasner's model are investigated. It is shown that the presence of scalar field in model is equivalent to metric in the spacetime with additional dimensions and we propose the idea of generating additional dimensions by massless scalar field. We propose a method of renormalization of metric that describes conversion from spacetime with scalar field to higher-dimensional spacetime. We obtain the expression for cosmological constant which depends on the initial conditions for anisotropic metric coefficients. Using the method of Bogolubov, we investigate the influence of anisotropic metric onto the cosmological birth of particles and obtain the effective mass of scalar field depending on the cosmological constant.
KNOTS IN THE SOLID TORUS UP TO 6 CROSSINGS
Authors: GABROVŠEK BOŠTJAN , MROCZKOWSKI MACIEJ
Published: May 2012

We classify non-affine, prime knots in the solid torus up to 6 crossings. We establish which of these are amphicheiral: almost all knots with symmetric Jones polynomial are amphicheiral, but in a few cases we use stronger invariants, such as HOMFLYPT and Kauffman skein modules, to show that some such knots are not amphicheiral. Examples of knots with the same Jones polynomial that are different in the HOMFLYPT skein module are presented. It follows from our computations, that the wrapping conjecture is true for all knots up to 6 crossings.
E1 STRENGTH IN LIGHT NUCLEI: SKYRME RPA ANALYSIS
Authors: KVASIL J. , REPKO A. , NESTERENKO V. O. , KLEINIG W. , REINHARD P.-G.
Published: May 2012

The giant dipole resonance (GDR) in N = 28 isotones (48Ca ,50Ti ,52Cr ,54Fe ) is analyzed in the framework of the Skyrme random-phase-approximation (RPA). Three Skyrme forces, SkM*, SLy6 and SV-bas, are used. The effects beyond RPA are simulated by the double folding procedure. We show that dipole strength exhibits a large collective shift, which testifies to a strong impact of the residual interaction and signals on considerable anharmonic effects. In52Cr , a significant pairing impact is found. For exception of50Ti , an acceptable agreement with the experiment data is obtained, which justifies the ability of Skyrme forces to describe GDR in light nuclei.
THE BAIL-OUT! POSITIVE POLITICAL ECONOMICS OF GREEK-TYPE CRISES IN THE EMU
Authors: FAHRHOLZ CHRISTIAN , WÓJCIK CEZARY
Published: May 2012

The Greek bail-out was highly controversial. An oft-heard assessment is that (i) the bail-out was a mistake, (ii) the political haggling over it was irrational. Contrary to this view, our analysis suggests that, given EMU's present political-economic set-up, (i) the bail-out was unavoidable and (ii) the lengthy process of political haggling leading to it was understandable. We have based our analysis on a political-economic, game-theoretic model that helps to understand why and how the parties involved in the Greek crisis arrived at the bail-out and on what conditions the final solution depended.
MEDIUM-TERM DETERMINANTS OF INTERNATIONAL INVESTMENT POSITIONS: THE ROLE OF STRUCTURAL POLICIES
Authors: FURCERI DAVIDE , GUICHARD STÉPHANIE , RUSTICELLI ELENA
Published: May 2012

This paper provides an empirical investigation of the medium-term determinants of international investment positions for a large sample of advanced and emerging economies. In addition to the usually considered drivers of foreign assets and liabilities, the analysis focuses on the role of structural policy indicators. Using cross-section and panel regression techniques the results suggest that structural policy settings are important medium-term drivers of capital flows, having a relatively large impact on gross and net foreign capital positions and on their composition. In particular, the results suggest that certain kinds of structural policy reform could help to narrow global imbalances, and to modify the composition of international capital flows towards more stable and productive sources.
TRAPPED SURFACES
Authors: SENOVILLA JOSÉ M. M.
Published: May 2012

I review the definition and types of (closed) trapped surfaces. Surprising global properties are shown, such as their "clairvoyance" and the possibility that they enter into flat portions of the spacetime. Several results on the interplay of trapped surfaces with vector fields and with spatial hypersurfaces are presented. Applications to the quasi-local definition of Black Holes are discussed, with particular emphasis set onto marginally trapped tubes, trapping horizons and the boundary of the region with closed trapped surfaces. Finally, the core of a trapped region is introduced, and its importance discussed.
PHYSICAL ASPECTS OF QUASI-LOCAL BLACK HOLE HORIZONS
Authors: NIELSEN ALEX B.
Published: May 2012

We discuss some of the physical aspects expected to be associated with black holes. These include Hawking radiation, horizon entropy and cosmic censorship. In particular we focus on whether these properties are more naturally associated to causally defined horizons or quasi-local horizons.
ON THE LATE-TIME EVOLUTION IN A TORSION COSMOLOGY
Authors: XI PING
Published: May 2012

In this paper, we study the late-time behavior of a torsion cosmology. We show that there is the late-time de Sitter attractor when the torsion parameter a1belongs to [Formula: see text], which indicates the late-time behaviors of torsion cosmology insensitive to the initial condition and thus alleviates the fine-tuning problem. Furthermore, we discuss the evolution of statefinder parameters for torsion cosmology in the four different ranges of a1, and find their typical characteristic different from the other cosmological models. Most of importance, we obtain three kinds of solutions with a constant affine scalar curvature and a kind of expression with the non-constant curvature. Using these expressions, we shall be able to predict the evolution over the late-time in torsion cosmology.
Fracture development and diagenesis of Torridon Group Applecross Formation, near An Teallach, NW Scotland: millennia of brittle deformation resilience?
Authors: Ellis Magdalena A. , Laubach S. E. , Eichhubl P. , Olson J. E. , Hargrove P.
Published: May 2012

The Late Proterozoic Torridon Group Applecross Formation in the foreland of the Moine Thrust Belt, NW Scotland, contains deformation bands, three fracture sets (from oldest to youngest A, B, and L) defined by orientation, crosscutting relations, and progressively less quartz cement in younger sets, and joints. Set A crosscuts deformation bands and strikes north–south. Set B has trimodal orientation defining three linked subsets that formed concurrently. Set L strike ranges from NE–SW to ENE–WSW, in parent crack–wing crack arrays that formed progressively; these are more abundant near small-displacement, oblique-slip faults that offset the overlying Cambrian Eriboll Formation and the Moine Thrust Belt. Applecross sandstones have low fracture abundance, possibly a consequence of low elastic moduli (Young’s modulus 2.3–17.0 GPa, most values <6.9 GPa) and moderate to high subcritical crack index (45–78), resulting from compacted soft lithic grains and clay-mineral cements. Low abundance contradicts models that postulate persistent incipient failure by subsurface fracture. The fracture sequence resembles that found in the overlying Cambrian Eriboll Formation quartzarenites, implying that no widespread late Proterozoic fracture sets exist in this part of the Applecross Formation, an uneventful record for a rock profoundly resistant to brittle deformation.
Biomolecular Simulation: A Computational Microscope for Molecular Biology
Authors: Dror Ron O. , Dirks Robert M. , Grossman J.P. , Xu Huafeng , Shaw David E.
Published: May 2012

Molecular dynamics simulations capture the behavior of biological macromolecules in full atomic detail, but their computational demands, combined with the challenge of appropriately modeling the relevant physics, have historically restricted their length and accuracy. Dramatic recent improvements in achievable simulation speed and the underlying physical models have enabled atomic-level simulations on timescales as long as milliseconds that capture key biochemical processes such as protein folding, drug binding, membrane transport, and the conformational changes critical to protein function. Such simulation may serve as a computational microscope, revealing biomolecular mechanisms at spatial and temporal scales that are difficult to observe experimentally. We describe the rapidly evolving state of the art for atomic-level biomolecular simulation, illustrate the types of biological discoveries that can now be made through simulation, and discuss challenges motivating continued innovation in this field.
Single-Molecule Views of Protein Movement on Single-Stranded DNA
Authors: Ha Taekjip , Kozlov Alexander G. , Lohman Timothy M.
Published: May 2012

The advent of new technologies allowing the study of single biological molecules continues to have a major impact on studies of interacting systems as well as enzyme reactions. These approaches (fluorescence, optical, and magnetic tweezers), in combination with ensemble methods, have been particularly useful for mechanistic studies of protein–nucleic acid interactions and enzymes that function on nucleic acids. We review progress in the use of single-molecule methods to observe and perturb the activities of proteins and enzymes that function on flexible single-stranded DNA. These include single-stranded DNA binding proteins, recombinases (RecA/Rad51), and helicases/translocases that operate as motor proteins and play central roles in genome maintenance. We emphasize methods that have been used to detect and study the movement of these proteins (both ATP-dependent directional and random movement) along the single-stranded DNA and the mechanistic and functional information that can result from detailed analysis of such movement.
ATP Utilization and RNA Conformational Rearrangement by DEAD-Box Proteins
Authors: Henn Arnon , Bradley Michael J. , De La Cruz Enrique M.
Published: May 2012

RNA helicase enzymes catalyze the in vivo folding and conformational re-arrangement of RNA. DEAD-box proteins (DBPs) make up the largest family of RNA helicases and are found across all phyla. DBPs are molecular motor proteins that utilize chemical energy in cycles of ATP binding, hydrolysis, and product release to perform mechanical work resulting in reorganization of cellular RNAs. DBPs contain a highly conserved motor domain helicase core. Auxiliary domains, enzymatic adaptations, and regulatory partner proteins contribute to the diversity of DBP function throughout RNA metabolism. In this review we focus on the current understanding of the DBP ATP utilization mechanism in rearranging and unwinding RNA structures. We discuss DBP structural properties, kinetic pathways, and thermodynamic features of nucleotide-dependent interactions with RNA. We highlight recent advances in the DBP field derived from biochemical and molecular biophysical investigations aimed at developing a quantitative mechanistic understanding of DBP molecular motor function.
Extending Microscopic Resolution with Single-Molecule Imaging and Active Control
Authors: Thompson Michael A. , Lew Matthew D. , Moerner W.E.
Published: May 2012

Superresolution imaging of biological structures provides information beyond the optical diffraction limit. One class of superresolution techniques uses the power of single fluorescent molecules as nanoscale emitters of light combined with emission control, variously described by the acronyms PALM/FPALM/STORM and many others. Even though the acronyms differ and refer mainly to different active-control mechanisms, the underlying fundamental principles behind these “pointillist” superresolution imaging techniques are the same. Circumventing the diffraction limit requires two key steps. The first step (superlocalization) is the detection and localization of spatially separated single molecules. The second step actively controls the emitting molecules to ensure a very low concentration of single emitters such that they do not overlap in any one imaging frame. The final image is reconstructed from time-sequential imaging and superlocalization of the single emitting labels decorating the structure of interest. The statistical, imaging, and active-control strategies for achieving superresolution imaging with single molecules are reviewed.
Mechanisms of Sec61/SecY-Mediated Protein Translocation Across Membranes
Authors: Park Eunyong , Rapoport Tom A.
Published: May 2012

The Sec61 or SecY channel, a universally conserved protein-conducting channel, translocates proteins across and integrates proteins into the eukaryotic endoplasmic reticulum (ER) membrane and the prokaryotic plasma membrane. Depending on channel-binding partners, polypeptides are moved by different mechanisms. In cotranslational translocation, the ribosome feeds the polypeptide chain directly into the channel. In posttranslational translocation, a ratcheting mechanism is used by the ER-lumenal chaperone BiP in eukaryotes, and a pushing mechanism is utilized by the SecA ATPase in bacteria. In prokaryotes, posttranslational translocation is facilitated through the function of the SecD/F protein. Recent structural and biochemical data show how the channel opens during translocation, translocates soluble proteins, releases hydrophobic segments of membrane proteins into the lipid phase, and maintains the barrier for small molecules.
How Should We Think About the Ribosome?
Authors: Moore Peter B.
Published: May 2012

In a few years we are likely to have structures for the ribosome in all the conformations it assumes during protein synthesis. The golden age of ribosome structure determination is thus drawing to a close, and as it does the focus in the field will shift from structure determination to understanding why the ribosome's structure changes the way it does as it performs its function. Thus in the future, kinetic and thermodynamic experiments will become increasingly important, and as they do, the field will have to start thinking about the dynamics of the ribosome far more carefully than it has in the past. The reasoning that underlies these assertions will be explained, and a more general issue explored, namely what can be said today about the modus operandi of the ribosome. What kind of a device is it?
Structural and Energetic Basis of Allostery
Authors: Hilser Vincent J. , Wrabl James O. , Motlagh Hesam N.
Published: May 2012

Allostery is a biological phenomenon of fundamental importance in regulation and signaling, and efforts to understand this process have led to the development of numerous models. In spite of individual successes in understanding the structural determinants of allostery in well-documented systems, much less success has been achieved in identifying a set of quantitative and transferable ground rules that provide an understanding of how allostery works. Are there organizing principles that allow us to relate structurally different proteins, or are the determinants of allostery unique to each system? Using an ensemble-based model, we show that allosteric phenomena can be formulated in terms of conformational free energies of the cooperative elements in a protein and the coupling interactions between them. Interestingly, the resulting allosteric ground rules provide a framework to reconcile observations that challenge purely structural models of site-to-site coupling, including (a) allostery in the absence of pathways of structural distortions, (b) allostery in the absence of any structural change, and (c) the ability of allosteric ligands to act as agonists under some circumstances and antagonists under others. The ensemble view of allostery that emerges provides insights into the energetic prerequisites of site-to-site coupling and thus into how allostery works.
Zero-Mode Waveguides for Single-Molecule Analysis
Authors: Zhu Paul , Craighead Harold G.
Published: May 2012

We review the optical properties, fabrication, and applications of zero-mode waveguides (ZMWs) for single-molecule studies. These simple nano-structures allow individual molecules to be isolated for optical analysis at high concentrations. Fluorescent species are observed in a sufficiently small volume that the average number of fluorescent molecules is less than one, even at concentrations high enough for biochemical reactions to proceed at normal rates. Arrays of such structures can also be engineered into systems for real-time analysis of large numbers of single-molecule reactions or binding events. We also review the integration of ZMWs in different optical configurations and microfluidic systems.
Metabolite Recognition Principles and Molecular Mechanisms Underlying Riboswitch Function
Authors: Serganov Alexander , Patel Dinshaw J.
Published: May 2012

Riboswitches are mRNA elements capable of modulating gene expression in response to specific binding by cellular metabolites. Riboswitches exert their function through the interplay of alternative ligand-free and ligand-bound conformations of the metabolite-sensing domain, which in turn modulate the formation of adjacent gene expression controlling elements. X-ray crystallography and NMR spectroscopy have determined three-dimensional structures of virtually all the major riboswitch classes in the ligand-bound state and, for several riboswitches, in the ligand-free state. The resulting spatial topologies have demonstrated the wide diversity of riboswitch folds and revealed structural principles for specific recognition by cognate metabolites. The available three-dimensional information, supplemented by structure-guided biophysical and biochemical experimentation, has led to an improved understanding of how riboswitches fold, what RNA conformations are required for ligand recognition, and how ligand binding can be transduced into gene expression modulation. These studies have greatly facilitated the dissection of molecular mechanisms underlying riboswitch action and should in turn guide the anticipated development of tools for manipulating gene regulatory circuits.
The Consequences of the Internet for Politics
Authors: Farrell Henry
Published: May 2012

Political scientists are only now beginning to come to terms with the importance of the Internet to politics. The most promising way to study the Internet is to look at the role that causal mechanisms such as the lowering of transaction costs, homophilous sorting, and preference falsification play in intermediating between specific aspects of the Internet and political outcomes. This will allow scholars to disentangle the relevant causal relationships and contribute to important present debates over whether the Internet exacerbates polarization in the United States, and whether social media helped pave the way toward the Arab Spring uprisings of 2011. Over time, ever fewer political scientists are likely to study the Internet as such, as it becomes more and more a part of everyday political life. However, integrating the Internet's effects with present debates over politics, and taking proper advantage of the extraordinary data that it can provide, requires good causal arguments and attention to their underlying mechanisms.
How (and Why) Is This Time Different? The Politics of Economic Crisis in Western Europe and the United States
Authors: Pontusson Jonas , Raess Damian
Published: May 2012

This article compares government responses to the Great Recession of 2008–2009 with government responses to recessions and other economic challenges in the period 1974–1982. We focus on five countries: France, Germany, Sweden, the United Kingdom, and the United States. Across these countries, we observe two broad shifts in crisis responses. First, governments have in the recent period eschewed heterodox crisis policies and relied more exclusively on fiscal stimulus. Second, tax cuts have become a more important component of fiscal stimulus while spending cuts have featured more prominently in governments' efforts to consolidate their fiscal position. We argue that crisis responses reflect the interests and power of domestic actors as well as external constraints and the nature of the economic problems at hand.
Formal Models of Bureaucracy
Authors: Gailmard Sean , Patty John W.
Published: May 2012

In the past decade, political science has witnessed a substantial amount of research using formal models to explicate the rationale for and effects of myriad aspects of bureaucratic institutions. Whereas previous waves of formal modeling on bureaucratic structure emphasized bureaucracy as a device for making policy commitments last, more recent formal research has grappled with information asymmetries and more explicitly considered the principal-agent relationship between bureaucracies and political authorities. We review several major recent themes in this literature, particularly the effects and development of bureaucratic hierarchies, the agency dilemmas inherent when policy-making authority is delegated to bureaucrats, and the effects of institutional structure on the development and sharing of expertise and capacity in bureaucracies.
Global Civil Society: The Progress of Post-Westphalian Politics
Authors: Dryzek John S.
Published: May 2012

Despite lingering ambiguity surrounding the concept, global civil society is acclaimed by those who think they belong to it, and validated by international governmental organizations seeking legitimation for their activities. Its enthusiasts believe global civil society presages a more congenial kind of politics that transcends the system of sovereign states. Its critics deride its unrepresentativeness and complicity in established power relations. The critics can be answered by more subtle accounts of representation and by highlighting contestatory practices. Appreciation of the promise and perils of global civil society requires moving beyond preconceptions rooted in dated ideas about civil society and democracy as they allegedly function within states. Irrespective of the sophistication of such post-Westphalian moves, global civil society remains contested terrain, involving interconnected political and intellectual disputes. International relations theory proves less useful than it should be in clarifying what is at stake. Democratic theory can be brought to bear, and this encounter sheds new light on what democracy itself can entail.
In From the Cold: Institutions and Causal Inference in Postcommunist Studies
Authors: Frye Timothy
Published: May 2012

Wrestling with basic problems of causal inference between institutions and outcomes has been a central focus of political science over the last decade, and as elsewhere in the discipline, scholars of postcommunism have begun to make some headway on these problems. Their efforts have not only advanced important debates about postcommunism, but also in many cases addressed long-standing concerns in political science. This is in itself a sign that after years on the periphery of political science prior to 1989, the study of politics and economics in postcommunist Eurasia has come in from the cold.
Using Roll Call Estimates to Test Models of Politics
Authors: Clinton Joshua D.
Published: May 2012

Measuring the preferences of political elites is critically important for analyzing the determinants and consequences of elite behavior. The decisions that elites make when casting roll call votes seem to provide an ideal opportunity for measuring elite preferences and testing theories of the political process. The fact that the resulting ideal points are a consequence of applying a statistical model to a model of individual choice, however, may affect their usefulness for measuring elite preferences and testing predictions regarding individual and collective decision making. When analyzing roll call votes, scholars should be mindful of how their decisions may affect the estimates from their analyses. I use simulations to illustrate how the nonrandom selection of roll calls may affect the ability to estimate ideal points that accurately reflect the preferences responsible for generating the observed votes, and I discuss work integrating the many models involved in the production and consumption of roll call estimates.
LGBT Politics and American Political Development
Authors: Valelly Richard M.
Published: May 2012

Although the rest of the American politics subfield has taken up many of the research challenges that LGBT (lesbian, gay, bisexual, and transgender) politics poses, there has been very little attention to LGBT politics within APD (American political development). Yet LGBT politics has deeply developmental and “state-centered” dynamics. Until the middle of the twentieth century, sexual orientation was simply not widely and deeply politicized in the United States. But abruptly, in a period of a decade and a half (roughly 1940–1955), national political and bureaucratic actors created a national sexuality regime that has taken 60 years of LGBT struggle to partly reverse. In seeking to substitute a different, overtly inclusive sexuality regime, LGBT citizens and their straight allies have initiated far-reaching changes in public policy, regulation of the workplace, and the institution of marriage. American politics has thus been developed by LGBT politics—and in the process, a fruitful research agenda has emerged.
Global Distributive Justice: Why Political Philosophy Needs Political Science
Authors: Blake Michael
Published: May 2012

The philosophical literature on global distributive justice has become both more substantive and more rigorous in recent years. This article surveys some recent positions within that literature and notes that the differences between them often involve different views about the empirical facts underlying global wealth and poverty. This suggests that some headway might be gained in arguments about global justice by a greater engagement between political philosophy and empirical political science.
Short-term exercise reduces markers of hepatocyte apoptosis in nonalcoholic fatty liver disease
Authors: Fealy Ciaran E. , Haus Jacob M. , Solomon Thomas P. J. , Pagadala Mangesh , Flask Chris A. , McCullough Arthur J. , Kirwan John P.
Published: May 2012

Increased hepatocyte apoptosis is a hallmark of nonalcoholic fatty liver disease (NAFLD) and contributes to the profibrogenic state responsible for the progression to nonalcoholic steatohepatitis (NASH). Strategies aimed at reducing apoptosis may result in better outcomes for individuals with NAFLD. We therefore examined the effect of a short-term exercise program on markers of apoptosis—plasma cytokeratin 18 (CK18) fragments, alanine aminotransferase (ALT), aspartate aminotransferase (AST), soluble Fas (sFas), and sFas ligand (sFasL)—in 13 obese individuals with NAFLD [body mass index 35.2 ± 1.2 kg/m2, >5% intrahepatic lipid (IHL) assessed by 1H-MR spectroscopy]. Exercise consisted of treadmill walking for 60 min/day on 7 consecutive days at ∼85% of maximal heart rate. Additionally, subjects underwent an oral glucose tolerance test and a maximal oxygen consumption (V̇o2max) test before and after the exercise intervention. The Matsuda index was used to assess insulin sensitivity. We observed significant decreases in CK18 fragments (558.4 ± 106.8 vs. 323.4 ± 72.5 U/l, P < 0.01) and ALT (30.2 ± 5.1 vs. 24.3 ± 4.8 U/l, P < 0.05), and an increase in whole body fat oxidation (49.3 ± 6.1 vs. 69.4 ± 7.1 mg/min, P < 0.05), while decreases in circulating sFasL approached statistical significance (66.5 ± 6.0 vs. 63.0 ± 5.7 pg/ml, P = 0.06), as did the relationship between percent change in circulating CK18 fragments and ALT (r = 0.55, P = 0.05). We also observed a significant correlation between changes in fat oxidation and circulating sFasL (rho = −0.65, P < 0.05). There was no change in IHL following the intervention (18.2 ± 2.5 vs. 17.5 ± 2.1%, NS). We conclude that short-term exercise reduces a circulatory marker of hepatocyte apoptosis in obese individuals with NAFLD and propose that changes in the proapoptotic environment may be mediated through improved insulin sensitivity and increased oxidative capacity.
Imaging for lung physiology: What do we wish we could measure?
Authors: Robertson H. Thomas , Buxton Richard B.
Published: May 2012

The role of imaging as a tool for investigating lung physiology is growing at an accelerating pace. Looking forward, we wished to identify unresolved issues in lung physiology that might realistically be addressed by imaging methods in development or imaging approaches that could be considered. The role of imaging is framed in terms of the importance of good spatial and temporal resolution and the types of questions that could be addressed as these technical capabilities improve. Recognizing that physiology is fundamentally a quantitative science, a recurring emphasis is on the need for imaging methods that provide reliable measurements of specific physiological parameters. The topics included necessarily reflect our perspective on what are interesting questions and are not meant to be a comprehensive review. Nevertheless, we hope that this essay will be a spur to physiologists to think about how imaging could usefully be applied in their research and to physical scientists developing new imaging methods to attack challenging questions imaging could potentially answer.
No change in myonuclear number during muscle unloading and reloading
Authors: Bruusgaard J. C. , Egner I. M. , Larsen T. K. , Dupre-Aucouturier S. , Desplanches D. , Gundersen K.
Published: May 2012

Muscle fibers are the cells in the body with the largest volume, and they have multiple nuclei serving different domains of cytoplasm. A large body of previous literature has suggested that atrophy induced by hindlimb suspension leads to a loss of “excessive” myonuclei by apoptosis. We demonstrate here that atrophy induced by hindlimb suspension does not lead to loss of myonuclei despite a strong increase in apoptotic activity of other types of nuclei within the muscle tissue. Thus hindlimb suspension turns out to be similar to other atrophy models such as denervation, nerve impulse block, and antagonist ablation. We discuss how the different outcome of various studies can be attributed to difficulties in separating myonuclei from other nuclei, and to systematic differences in passive properties between normal and unloaded muscles. During reload, after hindlimb suspension, a radial regrowth is observed, which has been believed to be accompanied by recruitment of new myonuclei from satellite cells. The lack of nuclear loss during unloading, however, puts these findings into question. We observed that reload led to an increase in cross sectional area of 59%, and fiber size was completely restored to the presuspension levels. Despite this notable growth there was no increase in the number of myonuclei. Thus radial regrowth seems to differ from de novo hypertrophy in that nuclei are only added during the latter. We speculate that the number of myonuclei might reflect the largest size the muscle fibers have had in its previous history.