bluuebunny/crossref_metadata_2025 huggingface dataset:
Do SEII Electrons Really Degrade SEM Image Quality?
Authors: Bernstein Gary H. , Carter Andrew D. , Joy David C.
Published: May 2012

Generally, in scanning electron microscopy (SEM) imaging, it is desirable that a high‐resolution image be composed mainly of those secondary electrons (SEs) generated by the primary electron beam, denoted SEI. However, in conventional SEM imaging, other, often unwanted, signal components consisting of backscattered electrons (BSEs), and their associated SEs, denoted SEII, are present; these signal components contribute a random background signal that degrades contrast, and therefore signal‐to‐noise ratio and resolution. Ideally, the highest resolution SEM image would consist only of the SEI component. In SEMs that use conventional pinhole lenses and their associated Everhart–Thornley detectors, the image is composed of several components, including SEI, SEII, and some BSE, depending on the geometry of the detector. Modern snorkel lens systems eliminate the BSEs, but not the SEIIs. We present a microfabricated diaphragm for minimizing the unwanted SEII signal components. We present evidence of improved imaging using a microlithographically generated pattern of Au, about 500 nm thick, that blocks most of the undesired signal components, leaving an image composed mostly of SEIs. We refer to this structure as a “spatial backscatter diaphragm.” SCANNING 35:1‐6, 2013. © 2012 Wiley Periodicals, Inc.
Hand‐Rearing and Sex Determination Tool for the Taveta Golden Weaver (Ploceus castaneiceps)
Authors: Breeding Shawnlei , Ferrie Gina M. , Schutz Paul , Leighty Katherine A. , Plassé Chelle
Published: May 2012

Improvements in the ability to hand‐rear birds in captivity have aided zoological institutions in the sustainable management of these species, and have provided opportunities to examine their physical growth in varying conditions. Monitoring the weight gain and development of chicks is an important aspect of developing a hand‐rearing protocol. In this paper we provide the institutional history for a colonial species of passerine, the Taveta golden weaver, at Disney's Animal Kingdom®, in order to demonstrate the methods of establishing a successful breeding program which largely incorporates hand‐rearing in management of the population. We also tested if we could accurately predict sex of chicks using weights collected on Day 14 during the hand‐rearing process. Using this tool, we were able to correctly determine sex before fledging in more than 83% of chicks. Early sex determination is important in captive species for genetic management and husbandry purposes. While genetic sexing can be expensive, we found that using growth curves to determine sex can be a reliable and cost‐effective tool for population management of a colonial passerine. Zoo Biol. 31:600‐608, 2012. © 2012 Wiley Periodicals, Inc.
Chemotherapy and molecular‐targeted treatment for unresectable hepatic metastases: a Japanese perspective
Authors: Shimada Yasuhiro
Published: May 2012

Liver metastasis from colorectal cancer has become a common disease associated with the increase of primary colorectal cancer in Japan. The standard treatment for resectable liver metastases is still complete liver resection. Recent advances in systemic chemotherapy have introduced another strategy, i.e., conversion chemotherapy, for patients with initially diagnosed unresectable liver metastases. The conversion rate after neo‐adjuvant chemotherapy is increasing with multidisciplinary approaches. Long‐term clinical data have not been established yet. Indications for liver resection after neo‐adjuvant chemotherapy; optimal chemotherapy regimens; and histological changes in the normal liver are important research issues for the future.
The Ethnic-Civic Dichotomy and the Explanation of National Self-Understanding
Authors: Jayet Cyril
Published: May 2012

In his paper Ethnicity as Cognition (2006), Rogers Brubaker held that cognitive psychology can enrich the understanding of the practices of categorisation that underpins ethnicity, nationhood and race. I shall argue that the philosophical debate concerning the different types of explanation in social sciences – the explanations based on reasons and the explanations based on causal mechanisms – can throw some light on this issue. To analyse beliefs requires use of both approaches. It can be shown with the classical opposition between an ethnic and a civic conception of national belonging which derives from a reason-based approach. The causal mechanism approach underlying cognitive psychology can offer alternative models accounting for national self-understanding, notably the prototype model of categorisation. I confront empirically these two theories – the ethnic civic dichotomy and the prototype model – using theisspdata from 2003 and evidence the advantages and shortcomings of each theory.
Methionine restriction affects the phenotypic and transcriptional response of rainbow trout (Oncorhynchus mykiss) to carbohydrate-enriched diets
Authors: Craig Paul M. , Moon Thomas W.
Published: May 2012

Mammalian studies report that methionine restriction (MR) as a dietary regimen extends life span, delays the onset of age-related diseases and enhances fat oxidation in obese subjects with metabolic syndromes. However, the underlying cellular signalling pathways are poorly understood. Rainbow trout (Oncorhynchus mykiss) is a glucose-intolerant species, providing an excellent model for the study of carbohydrate metabolism. MR diets in combination with 12 % (+/ − ) and 22 % (+/ − ) carbohydrate-rich meals were fed to rainbow trout for a period of 8 weeks and phenotypic and transcript expression changes in the liver and white muscle were assessed. Fish fed MR diets, irrespective of carbohydrate load, were shown to abolish the glucose-intolerant phenotype 6 h post-feeding. There was a distinct switch in glucose and glycogen content in the liver of fish fed MR diets, with a significantly higher concentration of glycogen, suggesting reduced glycolytic capacity. Transcriptional responses to MR demonstrated decreased expression of hepatic fatty acid synthase, sterol regulatory binding protein 1, PPARγ coactivator 1-α and PPARα, indicative of a reduction in thede novosynthesis of fatty acids and cholesterol, and a potential decrease in hepatic fat oxidative capacity. Muscle adenylate charge was depressed under MR, and increased expression of AMP-activated protein kinase α1 was detected, indicative of reduced energy availability. Total DNA methylation showed that carbohydrate load, rather than MR, dictated hypomethylation of genomic DNA. This is the first study which demonstrates that MR can abolish a glucose-intolerant phenotype in trout, and identifies trout as a suitable model for studying metabolic syndromes.
Detection of recurrent and primary acquired cholesteatoma with echo-planar diffusion-weighted magnetic resonance imaging
Authors: Evlice A , Tarkan Ö , Kiroğlu M , Biçakci K , Özdemir S , Tuncer Ü , Çekiç E
Published: May 2012

Objective:

To evaluate the diagnostic value of echo-planar diffusion-weighted magnetic resonance imaging in pre-operative detection of suspected primary acquired, residual and/or recurrent cholesteatoma.

Materials and methods:

Fifty-eight chronic otitis media patients with suspected cholesteatoma were thus evaluated two weeks pre-operatively, and divided into group one (41 patients, no previous surgery, suspected primary acquired cholesteatoma) and group two (17 patients, previous surgery, scheduled ‘second-look’ or revision surgery for suspected residual or recurrent cholesteatoma). Patients' operative, histopathology and radiological findings were compared.

Results:

Cholesteatoma was found in 63 per cent of group one patients and 58 per cent of group two patients at surgery. Histopathological examination of surgical specimens indicated that imaging accurately predicted the presence or absence of cholesteatoma in 90 per cent of group one (37/41; 23 true positives, 14 true negatives) and 76 per cent of group two (13/17; seven true positives, six true negatives). Three patients in both groups were false negative diagnoses and one patient in both groups was a false positive. The sensitivity, specificity, and positive and negative predictive values of echo-planar diffusion-weighted magnetic resonance imaging of cholesteatoma were respectively 88, 93, 95 and 82 per cent in group one and 70, 85, 87 and 66 per cent in group two.

Conclusion:

Echo-planar diffusion-weighted magnetic resonance imaging is a valuable technique with high sensitivity and specificity for cholesteatoma imaging.
Pre-dicting the Past, Re-membering the Present: Theorizing Memory in Complicite's Mnemonic
Authors: Casado-Gual Núria
Published: May 2012

In Mnemonic, a play conceived and directed by Simon McBurney and devised by Theatre de Complicite, words are not only time capsules in which different fictionalized memories are preserved, but also mnemonic objects in their own right. The playtext they conform acts, of course, as a reminder of the show that this British company created in 1999 for the Salzburg Festival, and that toured internationally again in 2002: at the same time, the published text of the work contains the perspectives and potential techniques from which the notion of memory – and of individual and collective forms of remembrance associated with it – can be explored and semiotized. Núria Casado-Gual's article looks at the dramaturgical strategies and theatrical techniques used by the company in their particular theatricalization of memory. Mnemonic, she contends, is not only relevant as an outstanding piece of contemporary theatre, but also as a ‘memorable’ text that helps us decipher our enigmatic selves in apparently oblivious and eroding postmodern times. Núria Casado-Gual lectures in English language, literature, and theatre at the University of Lleida, Catalonia, Spain. She is author of a PhD thesis on the the Caribbean playwright Edgar Nkosi White, and combines her academic work with creative theatrical projects as both playwright and performer with the company Nurosfera.
A Semi-Markov Multiple State Model for Reverse Mortgage Terminations
Authors: Ji Min , Hardy Mary , Li Johnny Siu-Hang
Published: May 2012

Reverse mortgages provide a mechanism for seniors to release the equity that has been built up in their home. At termination, the mortgagors are usually guaranteed to owe no more than the value of their property. The value of the reverse mortgage guarantee is heavily dependent on the maturity or termination date, which is uncertain. In this paper, we model reverse mortgage terminations using a semi-Markov multiple state model which incorporates three different modes of exit: death, entrance into a long-term care facility, and voluntary prepayment. We apply the proposed model specifically to develop the valuation formulas for roll-up mortgages in the UK and Home Equity Conversion Mortgages (HECMs) in the USA. We examine the significance of each mode of termination by valuing the contracts allowing progressively for each mode. On the basis of our model and assumptions, we find that both health related terminations and voluntary (non-health related) terminations significantly impact the contract value. In addition we analyze the premium structure for US reverse mortgage insurance, and demonstrate that premiums appear to be too high for some borrowers, and substantial cross-subsidies may result.
Modeling the foreshock sequence prior to the 2011, MW9.0 Tohoku, Japan, earthquake
Authors: Marsan D. , Enescu B.
Published: May 2012

The 2011 MW9.0 Tohoku earthquake, Japan, was preceded by a 2 day‐long foreshock sequence, initiated by a MW7.3 earthquake. We analyze this foreshock sequence, with the aim of detecting possible aseismic deformation transients that could have driven its evolution. Continuous broad‐band recordings at F‐net stations are processed to identify as exhaustive a set of mJMA > 1.2 earthquakes as possible. We moreover directly quantify with these recordings the changes in detection level associated with changes in seismic or environmental noise. This earthquake data set is then modeled, to show that the whole sequence can be readily explained without the need to invoke aseismic transients. The observation of a 3‐hour long low‐frequency noise increase, concurrent with an apparent migration of seismicity toward the epicenter of the impending MW9.0 mega‐thrust earthquake, however suggests that some premonitory slip could have played a role in loading the asperity which failure initiated the MW9.0 shock. We thus propose that this aseismic slip, if it really existed, had only a minor role in triggering and southward displacing the foreshock sequence, as compared to earthquake interaction mechanisms that allow earthquakes to trigger one another.
Morphology of sea ice pressure ridges in the northwestern Weddell Sea in winter
Authors: Tan Bing , Li Zhi‐jun , Lu Peng , Haas Christian , Nicolaus Marcel
Published: May 2012

To investigate the morphology and distribution of pressure ridges in the northwestern Weddell Sea, ice surface elevation profiles were measured by a helicopter‐borne laser altimeter during Winter Weddell Outflow Study with the German R/V Polarstern in 2006. An optimal cutoff height of 0.62 m, derived from the best fits between the measured and theoretical ridge height and spacing distributions, was first used to separate pressure ridges from other sea ice surface undulations. It was found that the measured ridge height distribution was well modeled by a negative exponential function, and the ridge spacing distribution by a lognormal function. Next, based on the ridging intensity Ri (the ratio of mean ridge sail height to mean spacing), all profiles were clustered into three regimes by an improved k‐means clustering algorithm: Ri ≤ 0.01, 0.01 < Ri ≤ 0.026, and Ri > 0.026 (denoted as C1, C2, and C3 respectively). Mean (and standard deviation) of sail height was 0.99 (±0.07) m in Regime C1, 1.12 (±0.06) m in C2, and 1.17 (±0.04) m in C3, respectively, while the mean spacings (and standard deviations) were 232 (±240) m, 54 (±20) m, and 31 (±5.6) m. These three ice regimes coincided closely with distinct sea ice regions identified in a satellite radar image, where C1 corresponded to the broken ice in the marginal ice zone and level ice formed in the Larsen Polynya, C2 corresponded to the deformed first‐ and second‐year ice formed by dynamic action in the center of the study region, and C3 corresponded to heavily deformed ice in the outflowing branch of the Weddell Gyre. The results of our analysis showed that the relationship between the mean ridge height and frequency was well modeled by a logarithmic function with a correlation coefficient of 0.8, although such correlation was weaker when considering each regime individually. The measured ridge height and frequency were both greater than those reported by others for the Ross Sea. Compared with reported values for other parts of the Antarctic, the present ridge heights were greater, but the ridge frequencies and ridging intensities were smaller than the most extreme of them. Meanwhile, average thickness of ridged ice in our study region was significantly larger than that of the Coastal Ross Sea showing the importance of deformation and ice age for ice conditions in the northwestern Weddell Sea.
Experimental and numerical findings on the long‐term evolution of migrating alternate bars in alluvial channels
Authors: Crosato Alessandra , Desta Frehiwot Beidmariam , Cornelisse John , Schuurman Filip , Uijttewaal Wim S. J.
Published: May 2012

Migrating alternate bars form in alluvial channels as a result of morphodynamic instability. Extensive literature can be found on their origin and short‐term development, but their long‐term evolution has been poorly studied so far. In particular, it is not clear whether migrating bars eventually reach a (dynamic) equilibrium, as in previous studies bars were observed to elongate with time. We studied the long‐term evolution of alternate bars by performing two independent long‐duration laboratory experiments and some numerical tests with a physics‐based depth‐averaged model. In a straight flume with constant water flow and sediment recirculation, migrating bars followed a cyclic variation. They became gradually longer and higher for a while, then quickly much shorter and lower. In one case, all migrating bars simultaneously vanished almost completely only to reform soon after. At the same time, steady bars, two to three times as long, progressively developed from upstream, gradually suppressing the migrating bars. We also observed simultaneous vanishing of migrating bars in an annular flume experiment, this time at intervals of 6–8 d. Numerical simulations of long alluvial channels with constant flow rate and fixed banks show periodic vanishing of a few migrating bars at a time, occurring at regular spacing. Under constant flow rates, migrating bars appear as a transition phenomenon of alluvial channels having a cyclic character. These observations, however, might hold only for certain morphodynamics conditions, which should be further investigated.
A rare foreshock sequence of the 20 January 2007 Odaesan, Korea, earthquake to measure the existence of preseismic velocity changes
Authors: Schaff David P. , Kim Won‐Young
Published: May 2012

Dilatancy theory and laboratory studies predict that there may be changes in the velocity of seismic waves in the Earth's crust preceding large earthquakes due to cracks opening up in response to stress changes. These changes, however, have been extremely difficult to find in the field. Because we do not know where or when the next earthquake will strike, often there is not sufficient instrumentation to capture such a signal if it exists with active sources. But natural sources such as repeating earthquakes offer hope of measuring a preseismic signal. To date, however, they have not measured a preseismic signal, perhaps due to insufficient temporal sampling, especially if the signal is short lived. We examine a rare foreshock sequence of nine near‐repeating events with fine temporal sampling all occurring within 3 days of the Mw 4.6 main shock with the last event occurring an hour before. The nearest event occurred within 114 m of the main shock hypocenter. This presents a unique opportunity to measure preseismic velocity changes at the depth of the main shock, which is 9.4 km. Because the foreshocks are not exact repeats, slight position differences bias the velocity change measurements. The locations of these events are known precisely, however, which allows for us to correct for these biases by treating the events as a source array, improving the measurement precision by up to an order of magnitude. We observe no apparent preseismic velocity change signal, but we are able to place an upper bound on its existence ranging from 0.01% to 0.08%.
The effects of artificial gender imbalance
Authors: Hesketh Therese , Min Jiang Min
Published: May 2012

The use of reproductive technology to service a preference for male offspring has created an artificial gender imbalance, notably in Asian countries. The social effects of this large surplus of young men are not yet clear, but concerted action might be necessary to address the problem
Lattice cluster theory of associating telechelic polymers. III. Order parameter and average degree of self-assembly, transition temperature, and specific heat
Authors: Dudowicz Jacek , Freed Karl F. , Douglas Jack F.
Published: May 2012

The lattice cluster theory of strongly interacting, structured polymer fluids is applied to determine the thermodynamic properties of solutions of telechelic polymers that may associate through bifunctional end groups. Hence, this model represents a significant albeit natural extension of a diverse array of prior popular equilibrium polymerization models in which structureless “bead” monomers associate into chain-like clusters under equilibrium conditions. In particular, the thermodynamic description of the self-assembly of linear telechelic chains in small molecule solvents (initiated in Paper II) is systematically extended through calculations of the order parameter Φ and average degree ⟨N⟩ of self-assembly, the self-assembly transition temperature Tp, and the specific heat CV of solutions of telechelic molecules. Special focus is placed on examining how molecular and thermodynamic parameters, such as the solution composition ϕ, temperature T, microscopic interaction energies (εs and ε), and length M of individual telechelic chains, influence the computed thermodynamic quantities that are commonly used to characterize self-assembling systems.
Generalized approach to the description of recombination kinetics in bulk heterojunction solar cells—extending from fully organic to hybrid solar cells
Authors: Conings Bert , Baeten Linny , Boyen Hans-Gerd , Spoltore Donato , D’Haen Jan , Van Bael Marlies K. , Manca Jean V.
Published: May 2012

Lately, research efforts in photovoltaics towards hybrid solar cells based on nanostructured metal oxides and conjugated polymers have been intensifying. However, very limited effort has been spent so far to investigate their recombination kinetics in comparison with their fully organic counterpart. In this work, impedance spectroscopy under different illumination intensities is used to probe the recombination kinetics of hybrid solar cells based on ZnO nanorod arrays and poly(3-hexylthiophene). A recombination-based model developed for fully organic solar cells is effectively applied in our hybrid solar cells, demonstrating their similarity in device physics and establishing the nanorod array/polymer compound as true bulk heterojunction.
Lorentz force sigmometry: A contactless method for electrical conductivity measurements
Authors: Uhlig Robert P. , Zec Mladen , Ziolkowski Marek , Brauer Hartmut , Thess André
Published: May 2012

The present communication reports a new technique for the contactless measurement of the specific electrical conductivity of a solid body or an electrically conducting fluid. We term the technique “Lorentz force sigmometry” where the neologism “sigmometry” is derived from the Greek letter sigma, often used to denote the electrical conductivity. Lorentz force sigmometry (LoFoS) is based on similar principles as the traditional eddy current testing but allows a larger penetration depth and is less sensitive to variations in the distance between the sensor and the sample. We formulate the theory of LoFoS and compute the calibration function which is necessary for determining the unknown electrical conductivity from measurements of the Lorentz force. We conduct a series of experiments which demonstrate that the measured Lorentz forces are in excellent agreement with the numerical predictions. Applying this technique to an aluminum sample with a known electrical conductivity of σAl=20.4MS/m and to a copper sample with σCu=57.92MS/m we obtain σAl=21.59MS/m and σCu=60.08MS/m, respectively. This demonstrates that LoFoS is a convenient and accurate technique that may find application in process control and thermo-physical property measurements for solid and liquid conductors.
Heating dynamics of CO2-laser irradiated silica particles with evaporative shrinking: Measurements and modeling
Authors: Elhadj S. , Qiu S. R. , Monterrosa A. M. , Stolz C. J.
Published: May 2012

The heating dynamics of CO2-laser heated micron-sized particles were determined for temperatures <3500 K measured using infrared imaging. A coupled mass and energy conservation model is derived to predict single particle temperatures and sizes, which were compared with data from particles deposited on non-absorbing substrates to assess the relevant heat transfer processes. Analysis reveals substrate conduction dominates all other heat losses, while laser absorption determined from Mie theory is strongly modulated by particle evaporative shrinking. This study provides insights into the light coupling and heating of particle arrays where the material optical properties are temperature-dependent and particle size changes are significant.
Effects of axial flow on the stability of a helical vortex tube
Authors: Hattori Y. , Fukumoto Y.
Published: May 2012

The effects of axial flow on the stability of a helical vortex tube are studied by short-wavelength stability analysis. By axial flow we mean the flow along the helical tube inside the vortex core. At the leading order the base flow is set to the Rankine vortex with uniform velocity along the helical tube. The exponential growth rate is obtained analytically as the magnitude of the sum of three O(ε) and five O(ε2) complex numbers, where ε is the ratio of the core to curvature radius. At O(ε) the effect of axial flow can be regarded as the effect of the Coriolis force; as a result the instability is the superposition of the curvature instability and the Coriolis or precessional instability since the two instabilities occur under the same resonance condition. At O(ε2) combined effects of the axial flow and the torsion appear; the maximum growth rate increases when the period of particle motion increases.
Temperature dependence of nanoscale friction for Fe on YBCO
Authors: Altfeder Igor , Krim Jacqueline
Published: May 2012

A magnetic probe microscopy study of levitation and atomic-scale friction is reported for Fe on YBCO (Tc = 92.5 K) in the temperature range 65–293 K. Below Tc, the friction coefficient is constant and exhibits no correlation with the strength of superconducting levitation forces. Above Tc, the friction coefficient increases progressively, and nearly doubles between Tc and room temperature. The results are discussed within the context of the underlying atomic-scale electronic and phononic mechanisms that give rise to friction, and it is concluded that contact electrification and static electricity may play a significant role in the non-superconducting phase. Given that the properties of YBCO can be finely tuned, the results point the way to a variety of interesting studies of friction and superconductors.
Dynamical band-engineering of spin-polarized edge-states in normal insulators
Authors: Wu B. H. , Liu Qin , Jiang Xunya , Cao J. C.
Published: May 2012

We investigate the electronic and transport properties of a normal insulator in form of a zigzag ribbon based on the Kane-Mele model subjected to circularly polarized radiation. Our results show that chiral edge-states can be induced in the band gap of the quasi-energy spectra under periodic driving. More interestingly, for appropriate parameters, there exists a single chiral edge state at each boundary of the sample. As a result, the conductance shows plateau structure with the step height e2/h as we increase the ac field intensity. These observations may find their potential applications for high-efficiency non-magnetic spin injection which can be readily tuned by modulating an external ac field.
Control of tensile strain in germanium waveguides through silicon nitride layers
Authors: Ghrib A. , de Kersauson M. , El Kurdi M. , Jakomin R. , Beaudoin G. , Sauvage S. , Fishman G. , Ndong G. , Chaigneau M. , Ossikovski R. , Sagnes I. , Boucaud P.
Published: May 2012

Germanium ridge waveguides can be tensilely strained using silicon nitride thin films as stressors. We show that the strain transfer in germanium depends on the width of the waveguides. Carrier population in the zone center Γ valley can also be significantly increased when the ridges are oriented along the 〈100〉 direction. We demonstrate an uniaxial strain transfer up to 1% observed on the room temperature direct band gap photoluminescence of germanium. The results are supported by 30 band k·p modeling of the electronic structure and the finite element modeling of the strain field.
Enhancement in coupling efficiency from laser to forward hot electrons by conical nanolayered targets
Authors: Yu Jinqing , Zhou Weimin , Cao Lihua , Zhao Zongqing , Cao Leifeng , Shan Lianqiang , Liu Dongxiao , Jin Xiaolin , Li Bin , Gu Yuqiu
Published: May 2012

To improve the energy coupling efficiency from laser to forward hot electrons, we propose a conical nanolayered target (CNT) and investigate by two-dimensional particle-in-cell simulations. Compared with nanolayered target, the energy coupling efficiency is enhanced from 34% to more than 68%. Detailed simulations indicate that this enhancement is attributed to both oblique incidence and focusing of the conical target. Moreover, CNT collimates the hot electrons better. The proposed target may serve as a new method for enhancing laser to forward hot electrons energy coupling efficiency.
Role for gene looping in intron-mediated enhancement of transcription
Authors: Moabbi Aboudi M. , Agarwal Neha , El Kaderi Belal , Ansari Athar
Published: May 2012

Intron-containing genes are often transcribed more efficiently than nonintronic genes. The effect of introns on transcription of genes is an evolutionarily conserved feature, being exhibited by such diverse organisms as yeast, plants, flies, and mammals. The mechanism of intron-mediated transcriptional activation, however, is not entirely clear. To address this issue, we inserted an intron in
INO1
, which is a nonintronic gene, and deleted the intron from
ASC1
, which contains a natural intron. We then compared transcription of
INO1
and
ASC1
genes in the presence and absence of an intron. Transcription of both genes was significantly stimulated by the intron. The introns have a direct role in enhancing transcription of
INO1
and
ASC1
because there was a marked increase in nascent transcripts from these genes in the presence of an intron. Intron-mediated enhancement of transcription required a splicing competent intron. Interestingly, both
INO1
and
ASC1
were in a looped configuration when their genes contained an intron. Intron-dependent gene looping involved a physical interaction of the promoter and the terminator regions. In addition, the promoter region interacted with the 5′ splice site and the terminator with the 3′ splice site. Intron-mediated enhancement of transcription was completely abolished in the looping defective
sua7-1
strain. No effect on splicing, however, was observed in
sua7-1
strain. On the basis of these results, we propose a role for gene looping in intron-mediated transcriptional activation of genes in yeast.
Global transcriptome response to ionic liquid by a tropical rain forest soil bacterium,Enterobacter lignolyticus
Authors: Khudyakov Jane I. , D’haeseleer Patrik , Borglin Sharon E. , DeAngelis Kristen M. , Woo Hannah , Lindquist Erika A. , Hazen Terry C. , Simmons Blake A. , Thelen Michael P.
Published: May 2012

To process plant-based renewable biofuels, pretreatment of plant feedstock with ionic liquids has significant advantages over current methods for deconstruction of lignocellulosic feedstocks. However, ionic liquids are often toxic to the microorganisms used subsequently for biomass saccharification and fermentation. We previously isolatedEnterobacter lignolyticusstrain SCF1, a lignocellulolytic bacterium from tropical rain forest soil, and report here that it can grow in the presence of 0.5 M 1-ethyl-3-methylimidazolium chloride, a commonly used ionic liquid. We investigated molecular mechanisms of SCF1 ionic liquid tolerance using a combination of phenotypic growth assays, phospholipid fatty acid analysis, and RNA sequencing technologies. Potential modes of resistance to 1-ethyl-3-methylimidazolium chloride include an increase in cyclopropane fatty acids in the cell membrane, scavenging of compatible solutes, up-regulation of osmoprotectant transporters and drug efflux pumps, and down-regulation of membrane porins. These findings represent an important first step in understanding mechanisms of ionic liquid resistance in bacteria and provide a basis for engineering microbial tolerance.
Comparative genomics of rhizobia nodulating soybean suggests extensive recruitment of lineage-specific genes in adaptations
Authors: Tian Chang Fu , Zhou Yuan Jie , Zhang Yan Ming , Li Qin Qin , Zhang Yun Zeng , Li Dong Fang , Wang Shuang , Wang Jun , Gilbert Luz B. , Li Ying Rui , Chen Wen Xin
Published: May 2012

The rhizobium–legume symbiosis has been widely studied as the model of mutualistic evolution and the essential component of sustainable agriculture. Extensive genetic and recent genomic studies have led to the hypothesis that many distinct strategies, regardless of rhizobial phylogeny, contributed to the varied rhizobium–legume symbiosis. We sequenced 26 genomes ofSinorhizobiumandBradyrhizobiumnodulating soybean to test this hypothesis. TheBradyrhizobiumcore genome is disproportionally enriched in lipid and secondary metabolism, whereas several gene clusters known to be involved in osmoprotection and adaptation to alkaline pH are specific to theSinorhizobiumcore genome. These features are consistent with biogeographic patterns of these bacteria. Surprisingly, no genes are specifically shared by these soybean microsymbionts compared with other legume microsymbionts. On the other hand, phyletic patterns of 561 known symbiosis genes of rhizobia reflected the species phylogeny of these soybean microsymbionts and other rhizobia. Similar analyses with 887 known functional genes or the whole pan genome of rhizobia revealed that only the phyletic distribution of functional genes was consistent with the species tree of rhizobia. Further evolutionary genetics revealed that recombination dominated the evolution of core genome. Taken together, our results suggested that faithfully vertical genes were rare compared with those with history of recombination including lateral gene transfer, although rhizobial adaptations to symbiotic interactions and other environmental conditions extensively recruited lineage-specific shell genes under direct or indirect control through the speciation process.
Deep brain stimulation of the ventral striatum enhances extinction of conditioned fear
Authors: Rodriguez-Romaguera Jose , Do Monte Fabricio H. M. , Quirk Gregory J.
Published: May 2012

Deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) reduces symptoms of intractable obsessive-compulsive disorder (OCD), but the mechanism of action is unknown. OCD is characterized by avoidance behaviors that fail to extinguish, and DBS could act, in part, by facilitating extinction of fear. We investigated this possibility by using auditory fear conditioning in rats, for which the circuits of fear extinction are well characterized. We found that DBS of the VS (the VC/VS homolog in rats) during extinction training reduced fear expression and strengthened extinction memory. Facilitation of extinction was observed for a specific zone of dorsomedial VS, just above the anterior commissure; stimulation of more ventrolateral sites in VS impaired extinction. DBS effects could not be obtained with pharmacological inactivation of either dorsomedial VS or ventrolateral VS, suggesting an extrastriatal mechanism. Accordingly, DBS of dorsomedial VS (but not ventrolateral VS) increased expression of a plasticity marker in the prelimbic and infralimbic prefrontal cortices, the orbitofrontal cortex, the amygdala central nucleus (lateral division), and intercalated cells, areas known to learn and express extinction. Facilitation of fear extinction suggests that, in accord with clinical observations, DBS could augment the effectiveness of cognitive behavioral therapies for OCD.
Photoprotection in a purple phototrophic bacterium mediated by oxygen-dependent alteration of carotenoid excited-state properties
Authors: Šlouf Václav , Chábera Pavel , Olsen John D. , Martin Elizabeth C. , Qian Pu , Hunter C. Neil , Polívka Tomáš
Published: May 2012

Carotenoids are known to offer protection against the potentially damaging combination of light and oxygen encountered by purple phototrophic bacteria, but the efficiency of such protection depends on the type of carotenoid.
Rhodobacter sphaeroides
synthesizes spheroidene as the main carotenoid under anaerobic conditions whereas, in the presence of oxygen, the enzyme spheroidene monooxygenase catalyses the incorporation of a keto group forming spheroidenone. We performed ultrafast transient absorption spectroscopy on membranes containing reaction center-light-harvesting 1-PufX (RC-LH1-PufX) complexes and showed that when oxygen is present the incorporation of the keto group into spheroidene, forming spheroidenone, reconfigures the energy transfer pathway in the LH1, but not the LH2, antenna. The spheroidene/spheroidenone transition acts as a molecular switch that is suggested to twist spheroidenone into an s-
trans
configuration increasing its conjugation length and lowering the energy of the lowest triplet state so it can act as an effective quencher of singlet oxygen. The other consequence of converting carotenoids in RC-LH1-PufX complexes is that S
2
/S
1
/
triplet
pathways for spheroidene is replaced with a new pathway for spheroidenone involving an activated intramolecular charge-transfer (ICT) state. This strategy for RC-LH1-PufX-spheroidenone complexes maintains the light-harvesting cross-section of the antenna by opening an active, ultrafast S
1
/ICT channel for energy transfer to LH1 Bchls while optimizing the triplet energy for singlet oxygen quenching. We propose that spheroidene/spheroidenone switching represents a simple and effective photoprotective mechanism of likely importance for phototrophic bacteria that encounter light and oxygen.
Nuclear factor of activated T cells (NFATc4) is required for BDNF-dependent survival of adult-born neurons and spatial memory formation in the hippocampus
Authors: Quadrato Giorgia , Benevento Marco , Alber Stefanie , Jacob Carolin , Floriddia Elisa M. , Nguyen Tuan , Elnaggar Mohamed Y. , Pedroarena Christine M. , Molkentin Jeffrey D. , Di Giovanni Simone
Published: May 2012

New neurons generated in the adult dentate gyrus are constantly integrated into the hippocampal circuitry and activated during encoding and recall of new memories. Despite identification of extracellular signals that regulate survival and integration of adult-born neurons such as neurotrophins and neurotransmitters, the nature of the intracellular modulators required to transduce those signals remains elusive. Here, we provide evidence of the expression and transcriptional activity of nuclear factor of activated T cell c4 (NFATc4) in hippocampal progenitor cells. We show that NFATc4 calcineurin-dependent activity is required selectively for survival of adult-born neurons in response to BDNF signaling. Indeed, cyclosporin A injection and stereotaxic delivery of the BDNF scavenger TrkB-Fc in the mouse dentate gyrus reduce the survival of hippocampal adult-born neurons in wild-type but not in NFATc4
−/−
mice and do not affect the net rate of neural precursor proliferation and their fate commitment. Furthermore, associated with the reduced survival of adult-born neurons, the absence of NFATc4 leads to selective defects in LTP and in the encoding of hippocampal-dependent spatial memories. Thus, our data demonstrate that NFATc4 is essential in the regulation of adult hippocampal neurogenesis and identify NFATc4 as a central player of BDNF–driven prosurvival signaling in hippocampal adult-born neurons.
Identification of a tetratricopeptide repeat-like domain in the nicastrin subunit of γ-secretase using synthetic antibodies
Authors: Zhang Xulun , Hoey Robert J. , Lin Guoqing , Koide Akiko , Leung Brenda , Ahn Kwangwook , Dolios Georgia , Paduch Marcin , Ikeuchi Takeshi , Wang Rong , Li Yue-Ming , Koide Shohei , Sisodia Sangram S.
Published: May 2012

The γ-secretase complex, composed of presenilin, anterior-pharynx-defective 1, nicastrin, and presenilin enhancer 2, catalyzes the intramembranous processing of a wide variety of type I membrane proteins, including amyloid precursor protein (APP) and Notch. Earlier studies have revealed that nicastrin, a type I membrane-anchored glycoprotein, plays a role in γ-secretase assembly and trafficking and has been proposed to bind substrates. To gain more insights regarding nicastrin structure and function, we generated a conformation-specific synthetic antibody and used it as a molecular probe to map functional domains within nicastrin ectodomain. The antibody bound to a conformational epitope within a nicastrin segment encompassing residues 245–630 and inhibited the processing of APP and Notch substrates in in vitro γ-secretase activity assays, suggesting that a functional domain pertinent to γ-secretase activity resides within this region. Epitope mapping and database searches revealed the presence of a structured segment, located downstream of the previously identified DAP domain (
D
YIGS
a
nd
p
eptidase; residues 261–502), that is homologous to a tetratricopeptide repeat (TPR) domain commonly involved in peptide recognition. Mutagenesis analyses within the predicted TPR-like domain showed that disruption of the signature helical structure resulted in the loss of γ-secretase activity but not the assembly of the γ-secretase and that Leu571 within the TPR-like domain plays an important role in mediating substrate binding. Taken together, these studies offer provocative insights pertaining to the structural basis for nicastrin function as a “substrate receptor” within the γ-secretase complex.
Molecular tracing of the emergence, adaptation, and transmission of hospital-associated methicillin-resistant
Staphylococcus aureus
Authors: McAdam Paul R. , Templeton Kate E. , Edwards Giles F. , Holden Matthew T. G. , Feil Edward J. , Aanensen David M. , Bargawi Hiba J. A. , Spratt Brian G. , Bentley Stephen D. , Parkhill Julian , Enright Mark C. , Holmes Anne , Girvan E. Kirsty , Godfrey Paul A. , Feldgarden Michael , Kearns Angela M. , Rambaut Andrew , Robinson D. Ashley , Fitzgerald J. Ross
Published: May 2012

Hospital-associated infections caused by methicillin-resistant
Staphylococcus aureus
(MRSA) are a global health burden dominated by a small number of bacterial clones. The pandemic EMRSA-16 clone (ST36-II) has been widespread in UK hospitals for 20 y, but its evolutionary origin and the molecular basis for its hospital association are unclear. We carried out a Bayesian phylogenetic reconstruction on the basis of the genome sequences of 87
S. aureus
isolates including 60 EMRSA-16 and 27 additional clonal complex 30 (CC30) isolates, collected from patients in three continents over a 53-y period. The three major pandemic clones to originate from the CC30 lineage, including phage type 80/81, Southwest Pacific, and EMRSA-16, shared a most recent common ancestor that existed over 100 y ago, whereas the hospital-associated EMRSA-16 clone is estimated to have emerged about 35 y ago. Our CC30 genome-wide analysis revealed striking molecular correlates of hospital- or community-associated pandemics represented by mobile genetic elements and nonsynonymous mutations affecting antibiotic resistance and virulence. Importantly, phylogeographic analysis indicates that EMRSA-16 spread within the United Kingdom by transmission from hospitals in large population centers in London and Glasgow to regional health-care settings, implicating patient referrals as an important cause of nationwide transmission. Taken together, the high-resolution phylogenomic approach used resulted in a unique understanding of the emergence and transmission of a major MRSA clone and provided molecular correlates of its hospital adaptation. Similar approaches for hospital-associated clones of other bacterial pathogens may inform appropriate measures for controlling their intra- and interhospital spread.
Instant spectral assignment for advanced decision tree-driven mass spectrometry
Authors: Bailey Derek J. , Rose Christopher M. , McAlister Graeme C. , Brumbaugh Justin , Yu Pengzhi , Wenger Craig D. , Westphall Michael S. , Thomson James A. , Coon Joshua J.
Published: May 2012

We have developed and implemented a sequence identification algorithm (
inSeq
) that processes tandem mass spectra in real-time using the mass spectrometer’s (MS) onboard processors. The
inSeq
algorithm relies on accurate mass tandem MS data for swift spectral matching with high accuracy. The instant spectral processing technology takes ∼16 ms to execute and provides information to enable autonomous, real-time decision making by the MS system. Using
inSeq
and its advanced decision tree logic, we demonstrate (
i
) real-time prediction of peptide elution windows
en masse
(∼3 min width, 3,000 targets), (
ii
) significant improvement of quantitative precision and accuracy (~3x boost in detected protein differences), and (
iii
) boosted rates of posttranslation modification site localization (90% agreement in real-time vs. offline localization rate and an approximate 25% gain in localized sites). The decision tree logic enabled by
inSeq
promises to circumvent problems with the conventional data-dependent acquisition paradigm and provides a direct route to streamlined and expedient targeted protein analysis.
Spatiotemporally separated antigen uptake by alveolar dendritic cells and airway presentation to T cells in the lung
Authors: Thornton Emily E. , Looney Mark R. , Bose Oishee , Sen Debasish , Sheppard Dean , Locksley Richard , Huang Xiaozhu , Krummel Matthew F.
Published: May 2012

Asthma pathogenesis is focused around conducting airways. The reasons for this focus have been unclear because it has not been possible to track the sites and timing of antigen uptake or subsequent antigen presentation to effector T cells. In this study, we use two-photon microscopy of the lung parenchyma and note accumulation of CD11b+ dendritic cells (DCs) around the airway after allergen challenge but very limited access of these airway-adjacent DCs to the contents of the airspace. In contrast, we observed prevalent transepithelial uptake of particulate antigens by alveolar DCs. These distinct sites are temporally linked, as early antigen uptake in alveoli gives rise to DC and antigen retention in the airway-adjacent region. Antigen-specific T cells also accumulate in the airway-adjacent region after allergen challenge and are activated by the accumulated DCs. Thus, we propose that later airway hyperreactivity results from selective retention of allergen-presenting DCs and antigen-specific T cells in airway-adjacent interaction zones, not from variation in the abilities of individual DCs to survey the lung.
Cannabinoids suppress inflammatory and neuropathic pain by targeting α3 glycine receptors
Authors: Xiong Wei , Cui Tanxing , Cheng Kejun , Yang Fei , Chen Shao-Rui , Willenbring Dan , Guan Yun , Pan Hui-Lin , Ren Ke , Xu Yan , Zhang Li
Published: May 2012

Certain types of nonpsychoactive cannabinoids can potentiate glycine receptors (GlyRs), an important target for nociceptive regulation at the spinal level. However, little is known about the potential and mechanism of glycinergic cannabinoids for chronic pain treatment. We report that systemic and intrathecal administration of cannabidiol (CBD), a major nonpsychoactive component of marijuana, and its modified derivatives significantly suppress chronic inflammatory and neuropathic pain without causing apparent analgesic tolerance in rodents. The cannabinoids significantly potentiate glycine currents in dorsal horn neurons in rat spinal cord slices. The analgesic potency of 11 structurally similar cannabinoids is positively correlated with cannabinoid potentiation of the α3 GlyRs. In contrast, the cannabinoid analgesia is neither correlated with their binding affinity for CB1 and CB2 receptors nor with their psychoactive side effects. NMR analysis reveals a direct interaction between CBD and S296 in the third transmembrane domain of purified α3 GlyR. The cannabinoid-induced analgesic effect is absent in mice lacking the α3 GlyRs. Our findings suggest that the α3 GlyRs mediate glycinergic cannabinoid-induced suppression of chronic pain. These cannabinoids may represent a novel class of therapeutic agents for the treatment of chronic pain and other diseases involving GlyR dysfunction.