bluuebunny/crossref_metadata_2025 huggingface dataset:
‘How Much Correction of Syntactic Errors Are There, Anyway?’1
Authors: Bock Kathryn
Published: June 2011

Speech errors are a traditional source of evidence about what speakers have to do, and what they occasionally fail to do, when they talk. In particular, the linguistic patterns in errors are theoretically informative for what they disclose about the language production process. Among the most notable regularities in errors is a strong tendency for the structures of sentences to remain stable when words move around. These stable structural properties provide the backdrop against which slips in speaking have been used to explain how sentences develop before they are produced. This article traces the outlines of speech‐error analysis and then turns the focus around to look explicitly at how impervious to error the syntactic properties of language are. The aim is to assess the value of systematic studies of syntactic error for tracing the unfolding of spoken language when people try to say what they mean.
How Not to Run a Political Campaign: The Failure of the Unionist Free Traders 1903–6*
Authors: CLAYTON HUW
Published: June 2011

In 1903, Joseph Chamberlain launched a campaign aimed at the economic and political union of portions of the British empire behind a system of tariffs. The attack on Britain's 60‐year‐old system of free trade led to a polarising of opinion and sparked fierce controversy in the political sphere. It also shattered the unity of the Unionist Party, dividing it into three factions. One faction supported Chamberlain's policy, a second a more moderate policy proposed by party leader, Arthur Balfour, and a third – the smallest – the fiscal status quo. This article concerns this last faction, its motivations, actions and effectiveness. It argues that its concern with parliamentary alliances and methods, rather than the mass campaigns that were launched by its fellow opponents of Chamberlain, not only meant it was always bound to fail in its objectives, but made the problems of the Unionist Party far worse than they might otherwise have been. It concludes that the main reason why it failed to stop, or even delay Chamberlain's domination of the Unionist Party, not to mention suffering serious electoral losses, was largely due to its own incompetence in failing to grasp the new reality of mass politics and the need for new political approaches to deal with it.
John Robinson's ‘State’ for the General Election of 1774
Authors: THOMAS PETER D.G.
Published: June 2011

This note prints two documents of the 1774 general election compiled by John Robinson, secretary to the treasury. One is a list of the old house of commons in the summer of 1774, prior to its dissolution. MPs are listed, from the government standpoint, as Pro, Hopeful, Doubtful and Con. The other document is a list of the constituencies with the same political designations for MPs, both for the existing house of commons and the expected new House: no names are given for actual or prospective MPs. The election saw an unusually large number of contests, with 183 seats at stake in 102 constituencies, a higher total than has hitherto been known.
High‐Pressure Effects on the Microstructure, Texture, and Color of White‐Brined Cheese
Authors: Koca N. , Balasubramaniam V.M. , Harper W.J.
Published: June 2011

Abstract:  White‐brined cheeses were subjected to high‐pressure processing (HPP) at 50, 100, 200, and 400 MPa at 22 °C for 5 and 15 min and ripened in brine for 60 d. The effects of pressure treatment on the chemical, textural, microstructural, and color were determined. HPP did not affect moisture, protein, and fat contents of cheeses. Similar microstructures were obtained for unpressurized cheese and pressurized cheeses at 50 and 100 MPa, whereas a denser and continuous structure was obtained for pressurized cheeses at 200 and 400 MPa. These microstructural changes exhibited a good correlation with textural changes. The 200 and 400 MPa treatments resulted in significantly softer, less springy, less gummy, and less chewy cheese. Finally, marked differences were obtained in a* and b* values at higher pressure levels for longer pressure‐holding time and were also supported by ΔE* values. The cheese became more greenish and yellowish with the increase in pressure level.

Practical Application:  The quality of cheese is the very important to the consumers. This study documented the pressure‐induced changes in selected quality attributes of semisoft and brine‐salted cheese. The results can help the food processors to have knowledge of the process parameters resulting in quality changes and to identify optimal process parameters for preserving pressure‐treated cheeses.
Staling of Cereal Bran Enriched Cakes and the Effect of an Endoxylanase Enzyme on the Physicochemical and Sensorial Characteristics
Authors: Lebesi Dimitra M. , Tzia Constantina
Published: June 2011

Abstract:  The staling of cakes enriched with untreated brans and endoxylanase‐treated brans was evaluated by monitoring the changes in physicochemical, thermal, and sensorial properties of cakes during 7‐d storage. Oat and rice bran were treated with different levels (0, 70, and 700 ppm) of an endoxylanase enzyme and added to cakes on 30% flour weight basis. Moisture losses, water activity, crumb firmness, starch retrogradation, and sensorial characteristics were used as staling indicators. Avrami‐type equations were efficiently used for modeling the starch retrogradation kinetics, while linear models most adequately described crumb firming kinetics. Cake staling induced an increase in crumb firmness and enthalpy of amylopectin retrogradation, and a decrease in crumb moisture and sensory quality and acceptability scores of cakes. Oat bran‐containing cakes better maintained their characteristics compared to the ones containing rice bran along the 7‐d storage. Endoxylanase treatment of brans delayed the changes naturally induced during staling in crumb moisture content, amylopectin retrogradation enthalpy, and crumb firmness in the respective cakes. Deterioration of the sensorial characteristics was slower for the cakes containing endoxylanase‐treated brans, as well. The level of endoxylanase treatment did not differentiate significantly (P < 0.05) any of the staling indicators. Overall, this study demonstrated that addition of endoxylanase‐treated brans can result in cakes with improved nutritional characteristics and increased shelf life.

Practical Application:  The results of the study show the potential of using enzymes to modify underutilized food sources that can be properly incorporated in baked goods, improving their nutritional value, their quality characteristics, and providing longer shelf life. The developed procedure and results can be utilized by the bakery industry to make high fiber and low cost bakery products with improved sensorial characteristics that are appealing to the consumers.
Characterization of Water Distribution in Xanthan‐Curdlan Hydrogel Complex Using Magnetic Resonance Imaging, Nuclear Magnetic Resonance Relaxometry, Rheology, and Scanning Electron Microscopy
Authors: Williams Patrick D. , Oztop Mecit Halil , McCarthy Michael J. , McCarthy Kathryn L. , Lo Y. Martin
Published: June 2011

Abstract:  Xanthan‐curdlan hydrogel complex (XCHC) has been shown capable of retaining moisture up to 5 freeze‐thaw cycles (FTCs); however, moisture distribution in the complex in relation to the hydrogel composition and structure remains uncharacterized. In the present study, magnetic resonance imaging (MRI), nuclear magnetic resonance (NMR) relaxometry, rheology, and scanning electron microscopy (SEM) were used to examine the effect of water distribution and interaction with 2.0% aqueous solutions of xanthan, curdlan, and XCHC consisting of equal amounts of both polysaccharides. A gel structure with an indication of syneresis was clearly seen in the MR image of curdlan alone, whereas the distribution of protons throughout xanthan and XCHC samples remained homogeneous and showed no detectable syneresis. The three‐dimensional network, indicated by frequency sweeps, of curdlan was responsible for curdlan's gel structure. The frequency sweep and slope of the storage modulus (G′) of XCHC was significantly closer to curdlan with higher elasticity and less dependency upon angular frequency than xanthan alone. The reduction in XCHC dynamic moduli (G′ and G″) compared to curdlan could be attributed to the formation of wavy layers instead of a fully cured three‐dimensional structure. Addition of xanthan to curdlan restricted XCHC spin–spin relaxation time (T2) to intermediate and slower exchange regimes, namely approximately 110 and 342 ms, respectively, promoting the polymer's interaction with water while inhibiting interpolymer interactions found in curdlan. A 3rd proton pool with the slowest T2 seen in curdlan was not found in XCHC, correlating to the absence of syneresis.

Practical Application:  The combination of texture measurements and discrete noninvasive techniques was found capable of providing insightful understanding of water distribution in a gel system. These techniques may be applied to other hydrogel complexes. The XCHC system investigated has the potential to enhance freeze‐thaw stability in frozen food products by minimizing syneresis due to undesirable temperature fluctuations during distribution and consumer application.
Follow Your Heart: Emotion Adaptively Influences Perception
Authors: Stefanucci Jeanine K. , Gagnon Kyle T. , Lessard David A.
Published: June 2011

The current review introduces a new program of research that suggests the perception of spatial layout is influenced by emotions. Though perceptual systems are often described as closed and insulated, this review presents research suggesting that a variety of induced emotions (e.g., fear, disgust, sadness) can produce changes in vision and audition. Thus, the perceptual system may be highly interconnected, allowing emotional information to influence perceptions that, in turn, influence cognition. The body of work presented here also suggests that emotion‐based changes in perception help us solve particular adaptive problems because emotion does not change all perceptions of the world. Taking the adaptive significance of emotion into account allows us to make predictions about when and how emotion influences perception.
The Importance of Being Emergent: A Theoretical Exploration of Impression Formation in Novel Social Category Conjunctions
Authors: Wood Chantelle , Hutter Russell R. C.
Published: June 2011

Social category conjunction is a form of multiple categorization involving the combination of two simultaneously salient constituent categories to form a complex category (e.g., female soldier). Research has reliably demonstrated that perceivers often apply emergent traits when forming impressions of novel incongruent social category conjunctions, that is, traits not associated with the simple constituent categories (e.g., Kunda, Miller, & Claire, 1990). However, the theoretical literature modeling the mechanisms underlying impression formation in novel social category conjunctions is less well established and inconsistent. In this article, we critically evaluate the current state of empirical research and theory on novel social category conjunction, with particular reference to emergent traits, aiming to provide a more coherent framework for future research and theory. In addition, we seek to emphasize the wider importance of emergent traits, by drawing out links between research and theory on social category conjunctions with broader perspectives of impression formation.
Integrating Terror Management Theory into Fear Appeal Research
Authors: Hunt David M. , Shehryar Omar
Published: June 2011

Fear appeal communications have sustained the interest of researchers for over a half century. The dominant paradigm guiding fear appeal research asserts that differences in level of fear lead to differences in the persuasiveness of a message. Research grounded in the level of fear perspective has produced equivocal results, failed to explain why fear appeals sometimes backfire, and has not provided an a priori explanation for who may reject fear appeal messages. By emphasizing differences between individuals’ responses to the fear of death versus the fear of physically or socially undesirable consequences, terror management theory (TMT) offers a complementary theoretical perspective that may overcome the shortcomings of extant fear appeal research. This article reviews extant theoretical approaches to fear appeal research and summarizes the central tenets of TMT. A comparison of extant theories to TMT suggests that incorporating TMT into future fear appeal research may improve both the explanatory and predictive power of fear appeal theories.
Mediation Analysis in Social Psychology: Current Practices and New Recommendations
Authors: Rucker Derek D. , Preacher Kristopher J. , Tormala Zakary L. , Petty Richard E.
Published: June 2011

A key aim of social psychology is to understand the psychological processes through which independent variables affect dependent variables in the social domain. This objective has given rise to statistical methods for mediation analysis. In mediation analysis, the significance of the relationship between the independent and dependent variables has been integral in theory testing, being used as a basis to determine (1) whether to proceed with analyses of mediation and (2) whether one or several proposed mediator(s) fully or partially accounts for an effect. Synthesizing past research and offering new arguments, we suggest that the collective evidence raises considerable concern that the focus on the significance between the independent and dependent variables, both before and after mediation tests, is unjustified and can impair theory development and testing. To expand theory involving social psychological processes, we argue that attention in mediation analysis should be shifted towards assessing the magnitude and significance of indirect effects.
Accreditation of emerging oral health professions: options for dental therapy education programs
Authors: Gelmon Sherril B. , Tresidder Anna Foucek
Published: June 2011

Objectives: The study explored the options for accreditation of educational programs to prepare a new oral health provider, the dental therapist.

Methods: A literature review and interviews of 10 content experts were conducted. The content experts represented a wide array of interests, including individuals associated with the various dental stakeholder organizations in education, accreditation, practice, and licensure, as well as representatives of non‐dental accrediting organizations whose experience could inform the study.

Results: Development of an educational accreditation program for an emerging profession requires collaboration among key stakeholders representing education, practice, licensure, and other interests. Options for accreditation of dental therapy education programs include establishment of a new independent accrediting agency; seeking recognition as a committee within the Commission on Accreditation of Allied Health Education Programs; or working with the Commission on Dental Accreditation (CODA) to create a new accreditation program within CODA. These options are not mutually exclusive, and more than one accreditation program could potentially exist.

Conclusions: An educational accreditation program is built upon a well‐defined field, where there is a demonstrated need for the occupation and for accreditation of educational programs that prepare individuals to enter that occupation. The fundamental value of accreditation is as one player in the overall scheme of improving the quality of higher education delivered to students and, ultimately, the delivery of health services. Leaders concerned with the oral health workforce will need to consider future directions and the potential roles of new oral health providers as they determine appropriate directions for educational accreditation for dental therapy.
Thiazide‐Induced Hyponatraemia: Epidemiology and Clues to Pathogenesis
Authors: Glover Mark , Clayton Jenny
Published: June 2011

Thiazide diuretics are one of the most widely used and cost‐effective classes of antihypertensive agents worldwide. Thiazides however have a significant side effect profile and are frequently insufficient to normalize blood pressure alone. Thiazide‐induced hyponatraemia (TIH) is a major adverse effect, affecting up to one in seven patients receiving these drugs. TIH is more common in females, the elderly and those of low body weight and may cause symptoms such as confusion, falls and seizures. It is a common cause of hospital admission in the elderly.

Although TIH occurs at least as frequently as hypokalaemia, much less is understood about the mechanism by which this occurs. Thiazides lower blood pressure by reducing the reabsorption of sodium from the distal nephron by inhibition of the NaCl cotransporter. The molecular mechanism by which this occurs together with the little known role of thiazides in regulating water reabsorbtion from the collecting ducts is discussed and the relevance to TIH evaluated.

TIH is highly reproducible by thiazide rechallenge suggesting there may be a genetic predisposition. Both targeted resequencing of candidate genes and genome wide association techniques offer promising strategies by which such genetic contributions may be investigated. The rewards for uncovering the molecular mechanisms underlying TIH and the regulation of distal nephron sodium and water absorption are significant; not only could it inform the design of better tolerated, more efficacious thiazide‐like antihypertensive agents but it may also facilitate the pharmacogenomic profiling of hypertensive patients to avoid thiazides in those likely to suffer adverse effects.
Urethral Sensations are Related to the Development of Detrusor Overactivity
Authors: YOKOYAMA Osamu , MIWA Yoshiji , OYAMA Nobuyuki , AOKI Yoshitaka , ITO Hideaki , TANASE Kazuya , ISHIDA Hirokazu , MATSUTA Yosuke , KUSUKAWA Naoya , YAMAUCHI Hiroki , TAKAHARA Noriko , WATANABE Nozomu , TSUCHIYAMA Katsuki , YOKOI Satoshi , AKINO Hironobu
Published: June 2011

Urgency is the core symptom of the overactive bladder symptom complex, but the underlying mechanisms are not fully understood. Clinical findings have led to the assumption that bladder outlet obstruction (BOO) caused by benign prostatic enlargement (BPE) induces storage symptoms and detrusor overactivity. Presumably, BOO by BPE accounts for urgency; however, urgency is not always caused by BOO. Sensory nerves in the wall of the urethra fire in response to urethral fluid flow, and this activity initiates bladder contractions in the quiescent bladder and augments ongoing contractions in the active bladder. In humans, prostatic urethral anesthesia results in significant increases in bladder capacity among BPH patients without neurological diseases, therefore sensory stimuli from an anatomically altered prostatic urethra has the possibility to induce urgency and detrusor overactivity. Studies in animals demonstrate the basis for an excitatory urethra to bladder reflex. Urethral stimulation by prostaglandin E2 induces an excitatory effect on micturition reflex by activation of C‐fiber afferent nerves. α1A‐adrenoceptor blocker has an inhibitory effect on the micturition reflex, suggesting excitatory urethra to bladder reflex is mediated by α1A‐adrenoceptor. Even if there is no obstruction, increase in urethral sensory due to BPE may induce the development of the detrusor overactivity.
Best practices for evaluation of bone marrow in nonclinical toxicity studies
Authors: Reagan William J. , Irizarry‐Rovira Armando , Poitout‐Belissent Florence , Bolliger Anne Provencher , Ramaiah Shashi K. , Travlos Greg , Walker Dana , Bounous Denise , Walter Gail ,   Bone Marrow Working Group of ASVCP/STP
Published: June 2011

Abstract:This manuscript is intended to provide a best practice approach to accurately and consistently assess toxicant‐induced bone marrow effects of test articles. In nonclinical toxicity studies, complete blood count data in conjunction with the histological examination of the bone marrow are recommended as the foundation for assessing the effect of test articles on the hematopoietic system. This approach alone can be used successfully in many studies. However, in some situations it may be necessary to further characterize effects on the different hematopoietic lineages, either by cytological or flow cytometric evaluation of the bone marrow. Both modalities can be used successfully, and which one is selected will depend on the expertise, preference of the facility, and the nature of the change in the bone marrow. Other specialized techniques such as clonogenic assays or electron microscopy are used rarely to further characterize hematotoxicity. The indications and techniques to successfully employ histological, cytological, or flow cytometric evaluation as well as clonogenic assays and electron microscopy are reviewed.William J. Reagan, Armando Irizarry‐Rovira, Florence Poitout‐Belissent, Anne Provencher Bolliger, Shashi K. Ramaiah, Greg Travlos, Dana Walker, Denise Bounous, and Gail Walter. "Best Practices for Evaluation of Bone Marrow in Nonclinical Toxicity Studies."Toxicologic Pathology(39.2) pp. 435‐448, copyright 2011 by The Author(s), Reprinted by Permission of SAGE Publications Inc.
Applying additive modelling and gradient boosting to assess the effects of watershed and reach characteristics on riverine assemblages
Authors: Maloney Kelly O. , Schmid Matthias , Weller Donald E.
Published: June 2011

1. Issues with ecological data (e.g. non‐normality of errors, nonlinear relationships and autocorrelation of variables) and modelling (e.g. overfitting, variable selection and prediction) complicate regression analyses in ecology. Flexible models, such as generalized additive models (GAMs), can address data issues, and machine learning techniques (e.g. gradient boosting) can help resolve modelling issues. Gradient boosted GAMs do both. Here, we illustrate the advantages of this technique using data on benthic macroinvertebrates and fish from 1573 small streams in Maryland, USA.

2. We assembled a predictor matrix of 15 watershed attributes (e.g. ecoregion and land use), 15 stream attributes (e.g. width and habitat quality) and location (latitude and longitude). We built boosted and conventionally estimated GAMs for macroinvertebrate richness and for the relative abundances of macroinvertebrates in the Orders Ephemeroptera, Plecoptera and Trichoptera (%EPT); individuals that cling to substrate (%Clingers); and individuals in the collector/gatherer functional feeding group (%Collectors). For fish, models were constructed for taxonomic richness, benthic species richness, biomass and the relative abundance of tolerant individuals (%Tolerant Fish).

3. For several of the responses, boosted GAMs had lower pseudo R2s than conventional GAMs for in‐sample data but larger pseudo R2s for out‐of‐bootstrap data, suggesting boosted GAMs do not overfit the data and have higher prediction accuracy than conventional GAMs. The models explained most variation in fish richness (pseudo R2 = 0·97), least variation in %Clingers (pseudo R2 = 0·28) and intermediate amounts of variation in the other responses (pseudo R2s between 0·41 and 0·60). Many relationships of macroinvertebrate responses to anthropogenic measures and natural watershed attributes were nonlinear. Fish responses were related to system size and local habitat quality.

4. For impervious surface, models predicted below model‐average macroinvertebrate richness at levels above c. 3·0%, lower %EPT above c. 1·5%, and lower %Clingers for levels above c. 2·0%. Impervious surface did not affect %Collectors or any fish response. Prediction functions for %EPT and fish richness increased linearly with log10 (watershed area), %Tolerant Fish decreased with log10 (watershed area), and benthic fish richness and biomass both increased nonlinearly with log10 (watershed area).

5. Gradient boosting optimizes the predictive accuracy of GAMs while preserving the structure of conventional GAMs, so that predictor–response relationships are more interpretable than with other machine learning methods. Boosting also avoids overfitting the data (by shrinking effect estimates towards zero and by performing variable selection), thus avoiding spurious predictor effects and interpretations. Thus, in many ecological settings, it may be reasonable to use boosting instead of conventional GAMs.
HERODOTUS AND SAMOS
Authors: PELLING CHRISTOPHER
Published: June 2011

What role does Samos play in Herodotus' narrative? Sometimes he shows the ‘warm sympathy’ that scholars have claimed, but more often Samian dysfunctionality is in point. Often events in Samos prepare for later episodes where Greek states offer more spirited, committed, or organised opposition to external threats; but the threat that they too might collapse into the Samian pattern is never far away. There are ways too in which Samos points forward to events beyond the end of Herodotus' text, especially the Samian defection from Athens in 440–39. It is difficult, though, to extract a single or simple moral from the Samian past for Herodotus' present; a series of conversations are reconstructed where very different conclusions could be drawn for events in the mid-430s and late-410s.
Influence of Channel Orientation on Heat Transfer in a Two-Pass Smooth and Ribbed Rectangular Channel (AR=2:1) Under Large Rotation Numbers
Authors: Huh Michael , Lei Jiang , Han Je-Chin
Published: June 2011

Experiments were conducted in a rotating two-pass cooling channel with an aspect ratio of 2:1 (Dh=16.9 mm). Results for two surface conditions are presented: smooth and one ribbed configurations. For the ribbed channel, the leading and trailing walls are roughened with ribs (P/e=10, e/Dh=0.094) and are placed at an angle (α=45 deg) to the mainstream flow. For each surface condition, two angles of rotation (β=90 deg,135 deg) were studied. For each angle of rotation, five Reynolds numbers (Re=10–40 K) were considered. At each Reynolds number, five rotational speeds (Ω=0–400 rpm) were considered. The maximum rotation number and buoyancy parameter reached were 0.45 and 0.85, respectively. Results showed that rotation effects are minimal in ribbed channels, at both angles of rotation, due to the strong interaction of rib and Coriolis induced vortices. In the smooth case, the channel orientation proved to be important and a beneficial heat transfer increase on the leading surface in the first pass (radially outward flow) was observed at high rotation numbers. The correlations developed in this study for predicting heat transfer enhancement due to rotation using the buoyancy parameter showed markedly good agreement with experimental data (±10%). Finally, heat transfer under rotating conditions on the tip cap showed to be quite dependent on channel orientation. The maximum tip cap Nu/Nus ratio observed was 2.8.
Modeling and Experiments of Buckling Modes and Deflection of Fixed-Guided Beams in Compliant Mechanisms
Authors: Holst Gregory L. , Teichert Gregory H. , Jensen Brian D.
Published: June 2011

This paper explores the deflection and buckling of fixed-guided beams used in compliant mechanisms. The paper’s main contributions include the addition of an axial deflection model to existing beam bending models, the exploration of the deflection domain of a fixed-guided beam, and the demonstration that nonlinear finite element models typically incorrectly predict a beam’s buckling mode unless unrealistic constraints are placed on the beam. It uses an analytical model for predicting the reaction forces, moments, and buckling modes of a fixed-guided beam undergoing large deflections. The model for the bending behavior of the beam is found using elliptic integrals. A model for the axial deflection of the buckling beam is also developed. These two models are combined to predict the performance of a beam undergoing large deflections including higher order buckling modes. The force versus displacement predictions of the model are compared to the experimental force versus deflection data of a bistable mechanism and a thermomechanical in-plane microactuator (TIM). The combined models show good agreement with the force versus deflection data for each device.
Vibration Amplitude in Rotary Ultrasonic Machining: A Novel Measurement Method and Effects of Process Variables
Authors: Cong W. L. , Pei Z. J. , Mohanty N. , Van Vleet E. , Treadwell C.
Published: June 2011

Rotary ultrasonic machining (RUM) has been used to machine both brittle and ductile materials as well as composite materials. There are numerous reported studies about the effects of various process variables on output responses. However, the current literature contains few articles about the measurement methods of vibration amplitude in RUM and about the effects of process variables on vibration amplitude. The lack of such knowledge has made it difficult to explain some experimentally observed phenomena in RUM and degraded the creditability of some experimental results with RUM. This paper, for the first time, presents a measurement method capable of measuring vibration amplitude during RUM machining. It also reports RUM experimental results on effects of cutting tool, ultrasonic power, workpiece material, tool rotation speed, and feedrate on ultrasonic amplitude. This study will fill some blanks in the literature and provide plausible explanations to some seemingly contradictory results reported in the literature.
Interaction Between Notch and Hif-α in Development and Survival of
Drosophila
Blood Cells
Authors: Mukherjee Tina , Kim William Sang , Mandal Lolitika , Banerjee Utpal
Published: June 2011

Ligand-independent Notch signaling promotes blood cell survival during normal development and under hypoxic stress.
Scaling Up Digital Circuit Computation with DNA Strand Displacement Cascades
Authors: Qian Lulu , Winfree Erik
Published: June 2011

Scalability and noise control are demonstrated in a molecular computer built from DNA.
Polariton Superfluids Reveal Quantum Hydrodynamic Solitons
Authors: Amo A. , Pigeon S. , Sanvitto D. , Sala V. G. , Hivet R. , Carusotto I. , Pisanello F. , Leménager G. , Houdré R. , Giacobino E , Ciuti C. , Bramati A.
Published: June 2011

A condensed-matter system is used to study superfluid dynamics.
Coupled, Circumferential Motions of the Cell Wall Synthesis Machinery and MreB Filaments in
B. subtilis
Authors: Garner Ethan C. , Bernard Remi , Wang Wenqin , Zhuang Xiaowei , Rudner David Z. , Mitchison Tim
Published: June 2011

Bacteria elongation involves moving synthetic complexes around the cell wall.
Behavior and the Dynamic Genome
Authors: Bell Alison M. , Robinson Gene E.
Published: June 2011

Does behavior evolve via gene expression changes in the brain in response to the environment?
Diminishing Returns Epistasis Among Beneficial Mutations Decelerates Adaptation
Authors: Chou Hsin-Hung , Chiu Hsuan-Chao , Delaney Nigel F. , Segrè Daniel , Marx Christopher J.
Published: June 2011

Interactions between genes reduce the benefits of a mutation and decrease the rate of fitness gain during adaptation.
The Worst Science in the World
An Empire of Ice
Scott, Shackleton, and the Heroic Age of Antarctic Science

by Edward J. Larson

Yale University Press, New Haven, CT, 2011. 358 pp. $28, £18.99. ISBN 9780300154085.
Authors: Smocovitis Vassiliki Betty
Published: June 2011

Emphasizing the importance of scientific research in early 20th-century British Antarctic expeditions, Larson argues for a new interpretation of the Scott-Amundsen race to the pole.
Detection of Convective Downflows in a Sunspot Penumbra
Authors: Scharmer G. B. , Henriques V. M. J. , Kiselman D. , Rodríguez J. de la Cruz
Published: June 2011

Downflows detected near the edges of a sunspot’s outer filaments provide a missing piece for convective models of sunspot motion.
Adult Neural Function Requires MeCP2
Authors: McGraw Christopher M. , Samaco Rodney C. , Zoghbi Huda Y.
Published: June 2011

An epigenetic program regulated by MeCP2 needs to be maintained throughout life for normal neurological function.
Clinical Significance of Interleukin-2/Gamma Interferon Ratios in Mycobacterium tuberculosis-Specific T-Cell Signatures
Authors: Suter-Riniker Franziska , Berger Antonia , Mayor Désirée , Bittel Pascal , Iseli Patricia , Bodmer Thomas
Published: June 2011

The simultaneous determination of interleukin-2 (IL-2) and gamma interferon (IFN-γ) in QuantiFERON-TB test plasma supernatants permitted the detection of shifts inMycobacterium tuberculosis-specific T-cell signatures. A subset of the 84 subjects tested revealed a significantly elevated IL-2/IFN-γ ratio, which may be a marker for the successful elimination ofM. tuberculosisinfection.
Practical Approach for Reliable Detection of AmpC Beta-Lactamase-Producing Enterobacteriaceae
Authors: Polsfuss Silke , Bloemberg Guido V. , Giger Jacqueline , Meyer Vera , Böttger Erik C. , Hombach Michael
Published: June 2011

In this prospective study allEnterobacteriaceaeisolates (n= 2,129) recovered in the clinical microbiology laboratory during October 2009 to April 2010 were analyzed for AmpC production. Clinical and Laboratory Standards Institute (CLSI) cefoxitin and cefotetan susceptibility breakpoints and CLSI critical ESBL diameters were used to screen for potential AmpC producers. In total, 305 isolates (211 potential AmpC producers and 94 AmpC screen-negative isolates as a control group) were further analyzed by multiplex PCR for the detection of plasmid-encodedampCbeta-lactamase genes and byampCpromoter sequence analysis (considered as the gold standard). Cefoxitin and cefotetan were assessed as primary screening markers. The sensitivities of cefoxitin and cefotetan for the detection of AmpC production were 97.4 and 52.6%, respectively, and the specificities were 78.7 and 99.3%, respectively. As a phenotypic confirmation test, the Etest AmpC and the cefoxitin-cloxacillin double-disk synergy method (CC-DDS) were compared. The sensitivities for the Etest AmpC and the CC-DDS method were 77.4 and 97.2%, respectively, and the specificity was 100% for both methods. The results of the Etest AmpC were inconclusive for 10 isolates. With the CC-DDS method 2 inconclusive results were observed. Based on this study, we propose a comprehensive diagnostic flow chart for the detection of AmpC production consisting of a simple phenotypic screening and a single phenotypic confirmation test with inconclusive results being resolved by molecular analysis. For the proposed flow chart using (i) cefoxitin as a screening marker for AmpC production, (ii) the CC-DDS method as phenotypic confirmation, and (iii) molecular methods in case of inconclusive results, the sensitivity and specificity for AmpC detection would have been 97.4 and 100%, respectively, with respect to the studied isolates. The phenotypic methods used in the AmpC algorithm are simple to perform and easy to implement in the diagnostic laboratory.
Evaluation of a New DNA Test for Detection of Carcinogenic Human Papillomavirus
Authors: Castle Philip E. , Gutierrez Erin C. , Leitch Sharon V. , Maus Courtney E. , McMillian Ray A. , Nussbaumer William A. , Vaughan Laurence M. , Wheeler Cosette M. , Gravitt Patti E. , Schiffman Mark
Published: June 2011

Using archived specimens, we evaluated a new automated real-time PCR assay (BD Diagnostics) that detects all carcinogenic human papillomaviruses (HPV) and provides HPV genotyping for seven of them, including HPV16 and HPV18, the two most carcinogenic HPV genotypes. We found comparable results with Hybrid Capture 2 (HC2) for detection of carcinogenic HPV (
n
= 473) and with Linear Array and Line Blot Assay (
n
= 371) for detection of individual HPV genotypes.
Comparative Evaluation of Combined-Disk Tests Using Different Boronic Acid Compounds for Detection of Klebsiella pneumoniae Carbapenemase-Producing Enterobacteriaceae Clinical Isolates
Authors: Tsakris Athanassios , Themeli-Digalaki Katerina , Poulou Aggeliki , Vrioni Georgia , Voulgari Evangelia , Koumaki Vasiliki , Agodi Antonella , Pournaras Spyros , Sofianou Danai
Published: June 2011

The accurate phenotypic detection of
Klebsiella pneumoniae
carbapenemase (KPC)-producing
Enterobacteriaceae
is an increasing necessity worldwide. We evaluated the performance of boronic acid combined-disk tests using as substrate imipenem or meropenem and as inhibitor of KPC production 300 μg aminophenylboronic acid (APBA), 600 μg APBA, or 400 μg phenylboronic acid (PBA). Tests were considered positive when an increase in the growth-inhibitory zone around a carbapenem disk with KPC inhibitor was 5 mm or greater of the growth-inhibitory zone diameter around the disk containing carbapenem alone. The comparison of the combined-disk tests was performed with 112 genotypically confirmed KPC-possessing
Enterobacteriaceae
isolates. To measure the specificity of the tests, 127 genotypically confirmed KPC-negative
Enterobacteriaceae
isolates that were nonsusceptible to at least one carbapenem were chosen for testing. Using disks containing imipenem without and with 300 μg APBA, 600 μg APBA, or 400 μg PBA, 72, 92, and 112 of the KPC producers, respectively, gave positive results (sensitivities, 64.3%, 82.1%, and 100%, respectively). Using disks containing meropenem without and with 300 μg APBA, 600 μg APBA, or 400 μg PBA, 87, 108, and 112 of the KPC producers, respectively, gave positive results (sensitivities, 77.7%, 96.4%, and 100%, respectively). Among KPC producers, the disk potentiation tests using meropenem and PBA demonstrated the largest differences in inhibition zones (
P
< 0.001). All combined-disk tests correctly identified 124 of the 127 non-KPC producers (specificity, 97.6%). This comparative study showed that PBA is the most effective inhibitor of KPC enzymes, and its use in combined-disk tests with meropenem may give the most easily interpreted results.
Use of Modified PCR Ribotyping for Direct Detection of Clostridium difficile Ribotypes in Stool Samples
Authors: Janežič Sandra , Štrumbelj Iztok , Rupnik Maja
Published: June 2011

PCR ribotyping was modified to allow direct detection of
Clostridium difficile
from stool samples. Direct PCR ribotyping was possible in 86 out of 99
C. difficile
-positive stool samples, and in 84 cases (84.8%), the ribotype determined directly from the stool sample was identical to the ribotype of the strain isolated from the same stool sample.
Evaluation of Two Molecular Assays for Rapid Detection of Mycobacterium tuberculosis Resistance to Fluoroquinolones in High-Tuberculosis and -Multidrug-Resistance Settings
Authors: Kontsevaya I. , Mironova S. , Nikolayevskyy V. , Balabanova Y. , Mitchell S. , Drobniewski F.
Published: June 2011

The Russian Federation is a high-tuberculosis (TB)-burden country with high rates of drug resistance, including multidrug and extensive drug resistance to TB (M/XDRTB). Rapid diagnosis of resistance to fluoroquinolones (FQs) using molecular assays is essential for the implementation of appropriate drug regimens and prevention of the transmission of XDR strains. A total of 51 individual MDRTB strains were tested by pyrosequencing of the quinolone resistance determining region of the
gyrA
gene and the GenoType MTBDR
sl
assay (Hain Lifescience, GmbH, Nehren, Germany), and the results were evaluated against those obtained by phenotypic drug susceptibility testing (DST). Mutations were detected in 25 (78.1%) FQ-resistant strains, with the majority of mutations (
n
= 19 [73.0%]) found in codon 94 of the
gyrA
gene; the novel mutation 1457 C→Τ was found in the
gyrB
gene. Three mixed allelic variants were detected, which is a well-known phenomenon in areas with high TB and drug-resistant TB rates. The sensitivity and specificity of pyrosequencing (86.2 and 100%, respectively) and MTBDR
sl
(86.2 and 100%, respectively) were high; however, the results for 5.9% of the analyzed strains were unreadable when MTBDR
sl
was used. The MTBDR
sl
and pyrosequencing assays offer a rapid and accurate means for diagnosing resistance to FQs in high-TB-burden areas.
Adenovirus Structural Protein IIIa Is Involved in the Serotype Specificity of Viral DNA Packaging
Authors: Ma Hsin-Chieh , Hearing Patrick
Published: June 2011

The packaging of the adenovirus (Ad) genome into a capsid displays serotype specificity. This specificity has been attributed to viral packaging proteins, the IVa2 protein and the L1-52/55K protein. We previously found that the Ad17 L1-52/55K protein was not able to complement the growth of an Ad5 L1-52/55K mutant virus, whereas two other Ad17 packaging proteins, IVa2 and L4-22K, could complement the growth of Ad5 viruses with mutations in the respective genes. In this report, we investigated why the Ad17 L1-52/55K protein was not able to complement the Ad5 L1-52/55K mutant virus. We demonstrate that the Ad17 L1-52/55K protein binds to the Ad5 IVa2 protein
in vitro
and the Ad5 packaging domain
in vivo
, activities previously associated with packaging function. The Ad17 L1-52/55K protein also associates with empty Ad5 capsids. Interestingly, we find that the Ad17 L1-52/55K protein is able to complement the growth of an Ad5 L1-52/55K mutant virus in conjunction with the Ad17 structural protein IIIa. The same result was found with the L1-52/55K and IIIa proteins of several other Ad serotypes, including Ad3 and Ad4. The Ad17 IIIa protein associates with empty Ad5 capsids. Consistent with the complementation results, we find that the IIIa protein interacts with the L1-52/55K protein
in vitro
and associates with the viral packaging domain
in vivo
. These results underscore the complex nature of virus assembly and genome encapsidation and provide a new model for how the viral genome may tether to the empty capsid during the encapsidation process.
Differentiated Neuroblastoma Cells Provide a Highly Efficient Model for Studies of Productive Varicella-Zoster Virus Infection of Neuronal Cells
Authors: Christensen Jenna , Steain Megan , Slobedman Barry , Abendroth Allison
Published: June 2011

Varicella-zoster virus (VZV) is a highly species-specific herpesvirus that targets sensory ganglionic neurons. This species specificity has limited the study of many aspects of VZV pathogenesis, including neuronal infection. We report development of a highly efficient neuroblastoma cell model to study productive VZV infection of neuronal cells. We show that differentiation of SH-SY5Y neuroblastoma cells yields a homogenous population of neuron-like cells that are permissive to the full VZV replicative cycle. These cells supported productive infection by both laboratory and clinical VZV isolates, including the live varicella vaccine. This model may enable rapid identification of genetic determinants facilitating VZV neurotropism.
Modulation of TRIM5α Activity in Human Cells by Alternatively Spliced TRIM5 Isoforms
Authors: Battivelli Emilie , Migraine Julie , Lecossier Denise , Matsuoka Saori , Perez-Bercoff Danielle , Saragosti Sentob , Clavel François , Hance Allan J.
Published: June 2011

TRIM5α is a restriction factor that can block an early step in the retroviral life cycle by recognizing and causing the disassembly of incoming viral capsids, thereby preventing the completion of reverse transcription. Numerous other isoforms of human TRIM5 exist, and isoforms lacking a C-terminal SPRY domain can inhibit the activity of TRIM5α. Thus, TRIM5α activity in a given cell type could be dependent on the relative proportions of TRIM5 isoforms expressed, but little information concerning the relative expression of TRIM5 isoforms in human cells is available. In this study, we demonstrate that mRNAs coding for TRIM5α represent only 50% of total TRIM5 transcripts in human cell lines, CD4
+
T cells, and macrophages. Transcripts coding for, in order of abundance, TRIM5ι (TRIM5-iota), a previously uncharacterized isoform, TRIM5γ, TRIM5δ, and TRIM5κ are also present. Like TRIM5γ and TRIM5δ, TRIM5ι and TRIM5κ do not inhibit HIV-1 replication, but both have dominant-negative activity against TRIM5α. Specific knockdown of TRIM5ι increases TRIM5α activity in human U373-X4 cells, indicating that physiological levels of expression of truncated TRIM5 isoforms in human cells can reduce the activity of TRIM5α.
The Herpes Simplex Virus 1 UL17 Protein Is the Second Constituent of the Capsid Vertex-Specific Component Required for DNA Packaging and Retention
Authors: Toropova Katerina , Huffman Jamie B. , Homa Fred L. , Conway James F.
Published: June 2011

The herpes simplex virus (HSV) UL17 and UL25 minor capsid proteins are essential for DNA packaging. They are thought to comprise a molecule arrayed in five copies around each of the capsid vertices. This molecule was initially termed the “C-capsid-specific component” (CCSC) (B. L. Trus et al., Mol. Cell
26:
479-489, 2007), but as we have subsequently observed this feature on reconstructions of A, B, and C capsids, we now refer to it more generally as the “capsid vertex-specific component” (CVSC) (S. K. Cockrell et al., J. Virol.
85:
4875-4887, 2011). We previously confirmed that UL25 occupies the vertex-distal region of the CVSC density by visualizing a large UL25-specific tag in reconstructions calculated from cryo-electron microscopy (cryo-EM) images. We have pursued the same strategy to determine the capsid location of the UL17 protein. Recombinant viruses were generated that contained either a small tandem affinity purification (TAP) tag or the green fluorescent protein (GFP) attached to the C terminus of UL17. Purification of the TAP-tagged UL17 or a similarly TAP-tagged UL25 protein clearly demonstrated that the two proteins interact. A cryo-EM reconstruction of capsids containing the UL17-GFP protein reveals that UL17 is the second component of the CVSC and suggests that UL17 interfaces with the other CVSC component, UL25, through its C terminus. The portion of UL17 nearest the vertex appears to be poorly constrained, which may provide flexibility in interacting with tegument proteins or the DNA-packaging machinery at the portal vertex. The exposed locations of the UL17 and UL25 proteins on the HSV-1 capsid exterior suggest that they may be attractive targets for highly specific antivirals.
Establishment of the Black-Tailed Prairie Dog (Cynomys ludovicianus) as a Novel Animal Model for Comparing Smallpox Vaccines Administered Preexposure in both High- and Low-Dose Monkeypox Virus Challenges
Authors: Keckler M. S. , Carroll D. S. , Gallardo-Romero N. F. , Lash R. R. , Salzer J. S. , Weiss S. L. , Patel N. , Clemmons C. J. , Smith S. K. , Hutson C. L. , Karem K. L. , Damon I. K.
Published: June 2011

The 2003 monkeypox virus (MPXV) outbreak and subsequent laboratory studies demonstrated that the black-tailed prairie dog is susceptible to MPXV infection and that the ensuing rash illness is similar to human systemic orthopoxvirus (OPXV) infection, including a 7- to 9-day incubation period and, likely, in some cases a respiratory route of infection; these features distinguish this model from others. The need for safe and efficacious vaccines for OPVX in areas where it is endemic or epidemic is important to protect an increasingly OPXV-naïve population. In this study, we tested current and investigational smallpox vaccines for safety, induction of anti-OPXV antibodies, and protection against mortality and morbidity in two MPXV challenges. None of the smallpox vaccines caused illness in this model, and all vaccinated animals showed anti-OPXV antibody responses and neutralizing antibody. We tested vaccine efficacy by challenging the animals with 10
5
or 10
6
PFU Congo Basin MPXV 30 days postvaccination and evaluating morbidity and mortality. Our results demonstrated that vaccination with either Dryvax or Acambis2000 protected the animals from death with no rash illness. Vaccination with IMVAMUNE also protected the animals from death, albeit with (modified) rash illness. Based on the results of this study, we believe prairie dogs offer a novel and potentially useful small animal model for the safety and efficacy testing of smallpox vaccines in pre- and postexposure vaccine testing, which is important for public health planning.