bluuebunny/crossref_metadata_2025 huggingface dataset:
Full functional activity of SSL7 requires binding of both complement C5 and IgA
Authors: Lorenz Natalie , Clow Fiona , Radcliff Fiona J , Fraser John D
Published: June 2013

Staphylococcus aureus is an opportunistic bacterial pathogen responsible for a range of diseases, from local skin infections through to life‐threatening illnesses such as toxic shock syndrome. S. aureus produces an assortment of molecules designed to evade or subvert the host immune system. One example is the 23 kDa staphylococcal superantigen‐like protein 7 (SSL7) that simultaneously binds immunoglobulin A (IgA) and complement C5 to inhibit complement‐mediated hemolytic and bactericidal activity. The avirulent bacterium Lactococcus lactis was engineered to express SSL7 so that its role in bacterial survival could be assessed without interference from other virulence factors. Expression of SSL7 by L. lactis led to significantly enhanced bacterial survival in whole human blood and prevented the membrane attack complex (C5b‐9) forming on the cell wall. To further understand the mechanism of action of SSL7, the activity of wild‐type SSL7 protein was compared with a panel of mutant proteins lacking the capacity to bind IgA, C5, or both IgA and C5. SSL7 potently inhibited in vitro chemotaxis of inflammatory myeloid cells in response to a pathogenic stimulus and when injected into mice, SSL7 blocked the migration of neutrophils into the peritoneum in response to an inoculum of heat‐killed S. aureus. Mutagenesis of the C5‐binding site on SSL7 abolished all inhibitory activity, while mutation of the IgA‐binding site had only partial effects, indicating that while IgA binding enhances activity it is not essential. SSL7 is an important staphylococcal virulence factor with potent anti‐inflammatory properties, which are mediated by targeting complement C5 and IgA.
Erratum: Dispersal in microbes: fungi in indoor air are dominated by outdoor air and show dispersal limitation at short distances
Authors: Adams Rachel I , Miletto Marzia , Taylor John W , Bruns Thomas D
Published: June 2013

Correction to: The ISME Journal (2013) 7, 1262–1273; doi:10.1038/ismej.2013.28; published online 21 February 2013 Since the publication of this article, the authors have noticed an error on Page 4, namely that the accession number contained within the first paragraph had been incorrectly listed as SRA059067 instead of SRA059097.
The transition state structure for coupled binding and folding of disordered protein domains
Authors: Dogan Jakob , Mu Xin , Engström Åke , Jemth Per
Published: June 2013

Intrinsically disordered proteins are abundant in the eukaryotic proteome and they are implicated in a range of different diseases. However, there is a paucity of experimental data on molecular details of the coupled binding and folding of such proteins. Two interacting and relatively well studied disordered protein domains are the activation domain from the p160 transcriptional co-activator ACTR and the nuclear co-activator binding domain (NCBD) of CREB binding protein. We have analyzed the transition state for their coupled binding and folding by protein engineering and kinetic experiments (Φ-value analysis) and found that it involves weak native interactions between the N-terminal helices of ACTR and NCBD, but is otherwise "disordered-like". Most native hydrophobic interactions in the interface between the two domains form later, after the rate-limiting barrier for association. Linear free energy relationships suggest a cooperative formation of native interactions, reminiscent of the nucleation-condensation mechanism in protein folding.
Hearing Conservation Program for Marching Band Members: A Risk for Noise-Induced Hearing Loss?
Authors: Jin Su-Hyun , Nelson Peggy B. , Schlauch Robert S. , Carney Edward
Published: June 2013

Purpose

To examine the risk for noise-induced hearing loss (NIHL) in university marching band members and to provide an overview of a hearing conservation program for a marching band.

Method

Sound levels during band rehearsals were recorded and audiometric hearing thresholds and transient otoacoustic emission were measured over a 3-year period. Musician's earplugs and information about hearing loss were provided to the students. The hearing thresholds of other college students were tested as a partial control.

Results

There were no significant differences in hearing thresholds between the two groups. During initial testing, more marching band members showed apparent high-frequency notches than control students. Follow-up hearing tests in a subsequent year for the marching band members showed that almost all notches disappeared. Persistent standard threshold shift (STS) across tests was not observed in the band members.

Conclusion

Band members showed no evidence of STS or persistent notched audiograms. Because accepted procedures for measuring hearing showed a lack of precision in reliably detecting early NIHL in marching band members, it is recommended that signs of NIHL be sought in repeated measurements compared to baseline audiograms rather than in a single measure (a single notch). A hearing conservation program for this population is still recommended because of lengthy rehearsal times with high sound-level exposure during rehearsals.
Performance-Intensity Functions of Mandarin Word Recognition Tests in Noise: Test Dialect and Listener Language Effects
Authors: Liu Danzheng , Shi Lu-Feng
Published: June 2013

Purpose

This study established the performance-intensity function for Beijing and Taiwan Mandarin bisyllabic word recognition tests in noise in native speakers of Wu Chinese. Effects of the test dialect and listeners' first language on psychometric variables (i.e., slope and 50%-correct threshold) were analyzed.

Method

Thirty-two normal-hearing Wu-speaking adults who used Mandarin since early childhood were compared to 16 native Mandarin-speaking adults. Both Beijing and Taiwan bisyllabic word recognition tests were presented at 8 signal-to-noise ratios (SNRs) in 4-dB steps (−12 dB to +16 dB). At each SNR, a half list (25 words) was presented in speech-spectrum noise to listeners' right ear. The order of the test, SNR, and half list was randomized across listeners. Listeners responded orally and in writing.

Results

Overall, the Wu-speaking listeners performed comparably to the Mandarin-speaking listeners on both tests. Compared to the Taiwan test, the Beijing test yielded a significantly lower threshold for both the Mandarin- and Wu-speaking listeners, as well as a significantly steeper slope for the Wu-speaking listeners.

Conclusion

Both Mandarin tests can be used to evaluate Wu-speaking listeners. Of the 2, the Taiwan Mandarin test results in more comparable functions across listener groups. Differences in the performance-intensity function between listener groups and between tests indicate a first language and dialectal effect, respectively.
Tool Kit for Screening Otologic Function of Older Adults1
Authors: Weinstein Barbara E.
Published: June 2013

Purpose

To propose a hearing health care tool kit, for use in primary care, that includes a new, comprehensive, and easy-to-administer self-report tool, namely, the Screening for Otologic Functional Impairments (SOFI). The target population for the proposed tool kit includes older adults with multimorbidity who are (a) at risk for hearing-related functional deficits and/or (b) likely to benefit from targeted audiologic interventions designed to optimize function, support independence, maximize safety, and cultivate self-sufficiency and social connectedness (American Academy of Nursing's Expert Panel on Acute and Critical Care, 2012).

Method

Twenty-nine older adults with varying levels of hearing impairment drawn from 2 ear, nose, and throat clinics and 1 university clinic underwent hearing testing and completed a series of self-report tools designed to assess otologic function and depression. All of the participants completed the SOFI on 2 occasions.

Results

The SOFI has high reliability and validity and the potential for identifying older adults requiring audiologic intervention.

Conclusion

The proposed tool kit, for use in primary care, includes several components that are integral to help-seeking behavior. The goal is to identify older adults with multimorbidity who are at risk for otologic conditions, that, once identified and treated, may help promote older adults' quality of care and life.
Adult Hearing Screening: Health Policy Issues—What Happens Next?
Authors: Davis Adrian , Smith Pauline
Published: June 2013

Purpose

Ten percent of adults in England have some type of hearing loss and would greatly benefit from hearing aids or other forms of hearing management. However, 76% of these adults do not have hearing aids or other management. The impact of this unmet need can be substantial and has been linked to depression, social isolation, employment problems, loss of independence, and dementia. This article explores how hearing screening—universal, targeted, or opportunistic—can address prevalent, incident, and future needs for hearing services as well as better define the extent of need.

Method

Adults age ≥60 years living at home in England took part in a health survey, part of which was to determine the extent of need for hearing services in this population. Survey methods included a face-to-face interview and hearing screening using pure tones as well as a self-report questionnaire on other health issues.

Results

The survey highlighted additional hearing-related factors that will enable referral decisions in primary care to be made with reasonable confidence that patients will use hearing aids and benefit from them. Some relevant nonhearing factors are also reported.

Conclusion

There is a growing aging population with increasing needs and expectations for hearing services. Targeted screening and triage in primary care, as well as use of advanced technologies, are discussed for the future.
Intelligibility of Clear Speech: Effect of Instruction
Authors: Lam Jennifer , Tjaden Kris
Published: June 2013

Purpose

The authors investigated how clear speech instructions influence sentence intelligibility.

Method

Twelve speakers produced sentences in habitual, clear, hearing impaired, and overenunciate conditions. Stimuli were amplitude normalized and mixed with multitalker babble for orthographic transcription by 40 listeners. The main analysis investigated percentage-correct intelligibility scores as a function of the 4 conditions and speaker sex. Additional analyses included listener response variability, individual speaker trends, and an alternate intelligibility measure: proportion of content words correct.

Results

Relative to the habitual condition, the overenunciate condition was associated with the greatest intelligibility benefit, followed by the hearing impaired and clear conditions. Ten speakers followed this trend. The results indicated different patterns of clear speech benefit for male and female speakers. Greater listener variability was observed for speakers with inherently low habitual intelligibility compared to speakers with inherently high habitual intelligibility. Stable proportions of content words were observed across conditions.

Conclusions

Clear speech instructions affected the magnitude of the intelligibility benefit. The instruction to overenunciate may be most effective in clear speech training programs. The findings may help explain the range of clear speech intelligibility benefit previously reported. Listener variability analyses suggested the importance of obtaining multiple listener judgments of intelligibility, especially for speakers with inherently low habitual intelligibility.
Deeper SSC estimator used as CDR
Authors: Zhang Yaming , Gai Weixin
Published: June 2013

A deeper SSC estimator used as a CDR with a low power mechanism based on third‐order architecture is proposed to suppress the disadvantage of the conventional third‐order CDR happening at the switching points of SSC (spread spectrum clocking). For 10 Gbit/s data speed, the depth of its SSC tracking may be up to 10000ppm at 30 kHz which helps to reduce more EMI.
Discrete Radon transform method for beam synthesis with arbitrarily configured antenna arrays in pulsed transmission mode
Authors: Basta N. , Dreher A.
Published: June 2013

A method for beam synthesis with arbitrarily configured transmitting pulsed antenna arrays based on the discrete Radon transform and its inverse is investigated. Remaining in the digital domain, by numerical means an optimal set of wave forms corresponding to the given array elements which allow for reconstruction of different time–space radiation masks is searched for. Simulation results are presented for the evaluation of the algorithm.
K‐band RF‐MEMS uniplanar reconfigurable‐bandwidth bandpass filter using multimodal immittance inverters
Authors: Contreras A. , Ribó M. , Pradell L. , Casals‐Terré J. , Giacomozzi F. , Iannacci J.
Published: June 2013

A K‐band RF‐MEMS uniplanar second‐order bandpass filter with reconfigurable bandwidth is presented. The filter is based on inductively‐coupled half‐wavelength slotline resonators and CPW‐slotline multimodal immittance inverters (MIIs). The coupling inductance and the MII length are reconfigured using RF‐MEMS ohmic‐contact switches. Experimental results show a 3 dB relative‐bandwidth change from 4.5 to 8.5% (maintaining a Butterworth response), and insertion losses of 5.2 and 3.7 dB for either state.
0.0012 mm2, 8 mW, single‐to‐differential converter with < 1.1% data cross error and < 3.4 ps RMS jitter up to 14 Gbit/s data rate
Authors: Chen Yong , Mak Pui‐In , Zhang Li , Qian He , Wang Yan
Published: June 2013

An extremely compact, doubly balancing single‐to‐differential converter (S2D) for high‐speed wireline systems is reported. It incorporates a two‐stage topology with ‘coarse balancing’ in the first stage and ‘fine balancing’ in the second stage by adopting a compact ‘positive‐feedback active inductor’ that simultaneously boosts the signal bandwidth. Fabricated in 65 nm CMOS, the S2D measures < 1.1% data cross error and < 3.4 ps RMS jitter up to a 14 Gbit/s data rate. The die occupies 0.0012 mm2 and consumes 8 mW.
Reduced‐complexity performance‐lossless (quasi‐)maximum‐likelihood detectors for S‐QAM modulated MIMO systems
Authors: Dai X. , Sun S. , Wang Y.
Published: June 2013

Proposed is a simplified branch metric calculation method for the (quasi‐)maximum‐likelihood (ML) detector for square quadrature amplitude modulation (S‐QAM) aided multiple‐input and multiple‐output (MIMO) multiplexing systems while retaining identical performance to the respective one. The key idea of the proposed method is to exploit the geometric property of the S‐QAM constellation, so that the branch metric calculation for all the constellation points can be calculated in an incremental way from any constellation point mainly through addition and bit‐shift, thus significantly reducing the computational complexity of the ML detector.
Physical‐contact‐type fan‐out device for multicore fibre
Authors: Abe Y. , Shikama K. , Yanagi S. , Takahashi T.
Published: June 2013

Demonstrated is a fan‐out device using small diameter fibres for 7‐core singlemode multicore fibre, which realises a compact size with ferrules and a split sleeve, and also achieves physical contact connection with an average connection loss of 0.17 dB and a return loss exceeding 49 dB.
Critical conditions of polymer chromatography: An insight from SCFT modeling
Authors: Yang Shuang , Neimark Alexander V.
Published: June 2013

In polymer chromatography, chain molecules are separated by molecular weight, size, and chemical composition due to adsorption and exclusion in nanoporous substrates. Three regimes of separation are distinguished depending on the adsorption strength and the pore size. In the regime of size exclusion chromatography, the adsorption energy is weak and the separation is entropy-driven with larger molecules having shorter retention times. On the opposite, in the regime of adsorption chromatography, enthalpy gain due to strong adsorption energy prevails over entropy loss, and the retention time of smaller molecules is shorter. We study the intermediate regime of so-called critical conditions, at which the entropic and enthalpic effects are mutually compensated, and the partition coefficient does not depend on the polymer molecular weight. Using the self-consistent field theory of tethered polymer chains, we confirm that for ideal chains the critical conditions are justified, albeit they depend on the pore size. However, for real chains with the excluded volume effect, the critical conditions hold only approximately, and the discrepancy increases as the pore size decreases. We show that it is important to consider three characteristic adsorption states: chains adsorbed at the external surface, chains adsorbed completely inside the pores, and partially translocated chains or “flowers” with a “root” adsorbed inside the pore and a “stem” hanging outside. The interplay of different adsorption mechanisms and the pore size distribution inherent to real substrates may lead to the manifestation of apparent critical adsorption conditions within the inherent deviation of experimental data.
Microsolvation in superfluid helium droplets studied by the electronic spectra of six porphyrin derivatives and one chlorine compound
Authors: Riechers R. , Pentlehner D. , Slenczka A.
Published: June 2013

After almost two decades of high resolution molecular spectroscopy in superfluid helium droplets, the understanding of microsolvation is still the subject of intense experimental and theoretical research. According to the published spectroscopic work including microwave, infrared, and electronic spectroscopy, the latter appears to be particularly promising to study microsolvation because of the appearance of pure molecular transitions and spectrally separated phonon wings. Instead of studying the very details of the influence of the helium environment for one particular dopant molecule as previously done for phthalocyanine, the present study compares electronic spectra of a series of non-polar porphyrin derivatives when doped into helium droplets consisting of 104–105 helium atoms. Thereby, we focus on the helium-induced fine structure, as revealed most clearly at the corresponding electronic origin. The interpretation and the assignment of particular features obtained in the fluorescence excitation spectra are based on additional investigations of dispersed emission spectra and of the saturation behavior. Besides many dopant-specific results, the experimental study provides strong evidence for a particular triple peak feature representing the characteristic signature of helium solvation for all seven related dopant species.
Influence of short range potential on field induced chain aggregation in low density dipolar particles
Authors: Richardi J. , Weis J.-J.
Published: June 2013

We investigate, by Monte Carlo simulation, the effect of the steepness of the short range repulsive potential on mesostructure formation in dipolar particles submitted to a strong external field. Columnar clusters made of several dipolar chains are only observed when the short-range potential is sufficiently steep. The confinement of the dipolar liquid in a slit geometry instead of bulk conditions suppresses the formation of columns.
Coupling density functional theory to polarizable force fields for efficient and accurate Hamiltonian molecular dynamics simulations
Authors: Schwörer Magnus , Breitenfeld Benedikt , Tröster Philipp , Bauer Sebastian , Lorenzen Konstantin , Tavan Paul , Mathias Gerald
Published: June 2013

Hybrid molecular dynamics (MD) simulations, in which the forces acting on the atoms are calculated by grid-based density functional theory (DFT) for a solute molecule and by a polarizable molecular mechanics (PMM) force field for a large solvent environment composed of several 103–105 molecules, pose a challenge. A corresponding computational approach should guarantee energy conservation, exclude artificial distortions of the electron density at the interface between the DFT and PMM fragments, and should treat the long-range electrostatic interactions within the hybrid simulation system in a linearly scaling fashion. Here we describe a corresponding Hamiltonian DFT/(P)MM implementation, which accounts for inducible atomic dipoles of a PMM environment in a joint DFT/PMM self-consistency iteration. The long-range parts of the electrostatics are treated by hierarchically nested fast multipole expansions up to a maximum distance dictated by the minimum image convention of toroidal boundary conditions and, beyond that distance, by a reaction field approach such that the computation scales linearly with the number of PMM atoms. Short-range over-polarization artifacts are excluded by using Gaussian inducible dipoles throughout the system and Gaussian partial charges in the PMM region close to the DFT fragment. The Hamiltonian character, the stability, and efficiency of the implementation are investigated by hybrid DFT/PMM-MD simulations treating one molecule of the water dimer and of bulk water by DFT and the respective remainder by PMM.
A simplified Tamm-Dancoff density functional approach for the electronic excitation spectra of very large molecules
Authors: Grimme Stefan
Published: June 2013

Two approximations in the Tamm-Dancoff density functional theory approach (TDA-DFT) to electronically excited states are proposed which allow routine computations for electronic ultraviolet (UV)- or circular dichroism (CD) spectra of molecules with 500–1000 atoms. Speed-ups compared to conventional time-dependent DFT (TD-DFT) treatments of about two to three orders of magnitude in the excited state part at only minor loss of accuracy are obtained. The method termed sTDA (“s” for simplified) employs atom-centered Löwdin-monopole based two-electron repulsion integrals with the asymptotically correct 1/R behavior and perturbative single excitation configuration selection. It is formulated generally for any standard global hybrid density functional with given Fock-exchange mixing parameter ax. The method performs well for two standard benchmark sets of vertical singlet-singlet excitations for values of ax in the range 0.2–0.6. The mean absolute deviations from reference data are only 0.2–0.3 eV and similar to those from standard TD-DFT. In three cases (two dyes and one polypeptide), good mutual agreement between the electronic spectra (up to 10–11 eV excitation energy) from the sTDA method and those from TD(A)-DFT is obtained. The computed UV- and CD-spectra of a few typical systems (e.g., C60, two transition metal complexes, [7]helicene, polyalanine, a supramolecular aggregate with 483 atoms and about 7000 basis functions) compare well with corresponding experimental data. The method is proposed together with medium-sized double- or triple-zeta type atomic-orbital basis sets as a quantum chemical tool to investigate the spectra of huge molecular systems at a reliable DFT level.
Zinc oxide inverse opal enzymatic biosensor
Authors: You Xueqiu , Pikul James H. , King William P. , Pak James J.
Published: June 2013

We report ZnO inverse opal- and nanowire (NW)-based enzymatic glucose biosensors with extended linear detection ranges. The ZnO inverse opal sensors have 0.01–18 mM linear detection range, which is 2.5 times greater than that of ZnO NW sensors and 1.5 times greater than that of other reported ZnO sensors. This larger range is because of reduced glucose diffusivity through the inverse opal geometry. The ZnO inverse opal sensors have an average sensitivity of 22.5 μA/(mM cm2), which diminished by 10% after 35 days, are more stable than ZnO NW sensors whose sensitivity decreased by 10% after 7 days.
Dense plasma heating and Gbar shock formation by a high intensity flux of energetic electrons
Authors: Ribeyre X. , Gus'kov S. , Feugeas J.-L. , Nicolaï Ph. , Tikhonchuk V. T.
Published: June 2013

Process of shock ignition in inertial confinement fusion implies creation of a high pressure shock with a laser spike having intensity of the order of a few PW/cm2. However, the collisional (Bremsstrahlung) absorption at these intensities is inefficient and a significant part of laser energy is converted in a stream of energetic electrons. The process of shock formation in a dense plasma by an intense electron beam is studied in this paper in a planar geometry. The energy deposition takes place in a fixed mass target layer with the areal density determined by the electron range. A self-similar isothermal rarefaction wave of a fixed mass describes the expanding plasma. Formation of a shock wave in the target under the pressure of expanding plasma is described. The efficiency of electron beam energy conversion into the shock wave energy depends on the fast electron energy and the pulse duration. The model is applied to the laser produced fast electrons. The fast electron energy transport could be the dominant mechanism of ablation pressure creation under the conditions of shock ignition. The shock wave pressure exceeding 1 Gbar during 200–300 ps can be generated with the electron pulse intensity in the range of 5–10 PW/cm2. The conclusions of theoretical model are confirmed in numerical simulations with a radiation hydrodynamic code coupled with a fast electron transport module.
Finite element modeling of acoustic wave propagation and energy deposition in bone during extracorporeal shock wave treatment
Authors: Wang Xiaofeng , Matula Thomas J. , Ma Yong , Liu Zheng , Tu Juan , Guo Xiasheng , Zhang Dong
Published: June 2013

It is well known that extracorporeal shock wave treatment is capable of providing a non-surgical and relatively pain free alternative treatment modality for patients suffering from musculoskeletal disorders but do not respond well to conservative treatments. The major objective of current work is to investigate how the shock wave (SW) field would change if a bony structure exists in the path of the acoustic wave. Here, a model of finite element method (FEM) was developed based on linear elasticity and acoustic propagation equations to examine SW propagation and deflection near a mimic musculoskeletal bone. High-speed photography experiments were performed to record cavitation bubbles generated in SW field with the presence of mimic bone. By comparing experimental and simulated results, the effectiveness of FEM model could be verified and strain energy distributions in the bone were also predicted according to numerical simulations. The results show that (1) the SW field will be deflected with the presence of bony structure and varying deflection angles can be observed as the bone shifted up in the z-direction relative to SW geometric focus (F2 focus); (2) SW deflection angels predicted by the FEM model agree well with experimental results obtained from high-speed photographs; and (3) temporal evolutions of strain energy distribution in the bone can also be evaluated based on FEM model, with varied vertical distance between F2 focus and intended target point on the bone surface. The present studies indicate that, by combining MRI/CT scans and FEM modeling work, it is possible to better understand SW propagation characteristics and energy deposition in musculoskeletal structure during extracorporeal shock wave treatment, which is important for standardizing the treatment dosage, optimizing treatment protocols, and even providing patient-specific treatment guidance in clinic.
Stoichiometry control of the electronic properties of the LaAlO3/SrTiO3 heterointerface
Authors: Sato H. K. , Bell C. , Hikita Y. , Hwang H. Y.
Published: June 2013

We investigate the effect of the laser parameters of pulsed laser deposition on the film stoichiometry and electronic properties of LaAlO3/SrTiO3 (001) heterostructures. The La/Al ratio in the LaAlO3 films was varied widely from 0.88 to 1.15, and was found to have a strong effect on the interface conductivity. In particular, the carrier density is modulated over more than two orders of magnitude. The film lattice expansion, caused by cation vacancies, is found to be the important functional parameter. These results can be understood to arise from the variations in the electrostatic boundary conditions, and their resolution, with stoichiometry.
Carbon-doped GaAs single junction solar microcells grown in multilayer epitaxial assemblies
Authors: Kang Dongseok , Arab Shermin , Cronin Stephen B. , Li Xiuling , Rogers John A. , Yoon Jongseung
Published: June 2013

A stack design for carbon-doped GaAs single junction solar microcells grown in triple-layer epitaxial assemblies is presented. As-grown materials exhibit improved uniformity of photovoltaic performance compared to zinc-doped systems due to the lack of mobile dopants while a slight degradation exists in middle and bottom devices. Detailed electrical and optical characterizations of devices together with systematic studies of acceptor reactivation reveal carbon-related defects accompanied by carrier compensation, and associated scattering and recombination centers are primarily responsible for the degraded contact properties and photovoltaic performance, resulting from prolonged thermal treatments of early-grown materials during the multilayer epitaxial growth.
Effect of substrate on thermoelectric properties of Al-doped ZnO thin films
Authors: Mele P. , Saini S. , Honda H. , Matsumoto K. , Miyazaki K. , Hagino H. , Ichinose A.
Published: June 2013

We have prepared 2% Al doped ZnO (AZO) thin films on SrTiO3 (STO) and Al2O3 substrates by Pulsed Laser Deposition technique at various deposition temperatures (Tdep = 300 °C–600 °C). Transport and thermoelectric properties of AZO thin films were studied in low temperature range (300 K–600 K). AZO/STO films present superior performance respect to AZO/Al2O3 films deposited at the same temperature, except for films deposited at 400 °C. Best film is the fully c-axis oriented AZO/STO deposited at 300 °C, which epitaxial strain and dislocation density are the lowest: electrical conductivity 310 S/cm, Seebeck coefficient −65 μV/K, and power factor 0.13 × 10−3 W m−1 K−2 at 300 K. Its performance increases with temperature. For instance, power factor is enhanced up to 0.55 × 10−3 W m−1 K−2 at 600 K, surpassing the best AZO film previously reported in literature.
Self-organization of bacterial biofilms is facilitated by extracellular DNA
Authors: Gloag Erin S. , Turnbull Lynne , Huang Alan , Vallotton Pascal , Wang Huabin , Nolan Laura M. , Mililli Lisa , Hunt Cameron , Lu Jing , Osvath Sarah R. , Monahan Leigh G. , Cavaliere Rosalia , Charles Ian G. , Wand Matt P. , Gee Michelle L. , Prabhakar Ranganathan , Whitchurch Cynthia B.
Published: June 2013

Twitching motility-mediated biofilm expansion is a complex, multicellular behavior that enables the active colonization of surfaces by many species of bacteria. In this study we have explored the emergence of intricate network patterns of interconnected trails that form in actively expanding biofilms of
Pseudomonas aeruginosa
. We have used high-resolution, phase-contrast time-lapse microscopy and developed sophisticated computer vision algorithms to track and analyze individual cell movements during expansion of
P. aeruginosa
biofilms. We have also used atomic force microscopy to examine the topography of the substrate underneath the expanding biofilm. Our analyses reveal that at the leading edge of the biofilm, highly coherent groups of bacteria migrate across the surface of the semisolid media and in doing so create furrows along which following cells preferentially migrate. This leads to the emergence of a network of trails that guide mass transit toward the leading edges of the biofilm. We have also determined that extracellular DNA (eDNA) facilitates efficient traffic flow throughout the furrow network by maintaining coherent cell alignments, thereby avoiding traffic jams and ensuring an efficient supply of cells to the migrating front. Our analyses reveal that eDNA also coordinates the movements of cells in the leading edge vanguard rafts and is required for the assembly of cells into the “bulldozer” aggregates that forge the interconnecting furrows. Our observations have revealed that large-scale self-organization of cells in actively expanding biofilms of
P. aeruginosa
occurs through construction of an intricate network of furrows that is facilitated by eDNA.
Numerical ability predicts mortgage default
Authors: Gerardi Kristopher , Goette Lorenz , Meier Stephan
Published: June 2013

Unprecedented levels of US subprime mortgage defaults precipitated a severe global financial crisis in late 2008, plunging much of the industrialized world into a deep recession. However, the fundamental reasons for why US mortgages defaulted at such spectacular rates remain largely unknown. This paper presents empirical evidence showing that the ability to perform basic mathematical calculations is negatively associated with the propensity to default on one’s mortgage. We measure several aspects of financial literacy and cognitive ability in a survey of subprime mortgage borrowers who took out loans in 2006 and 2007, and match them to objective, detailed administrative data on mortgage characteristics and payment histories. The relationship between numerical ability and mortgage default is robust to controlling for a broad set of sociodemographic variables, and is not driven by other aspects of cognitive ability. We find no support for the hypothesis that numerical ability impacts mortgage outcomes through the choice of the mortgage contract. Rather, our results suggest that individuals with limited numerical ability default on their mortgage due to behavior unrelated to the initial choice of their mortgage.
Cell geometric constraints induce modular gene-expression patterns via redistribution of HDAC3 regulated by actomyosin contractility
Authors: Jain Nikhil , Iyer K. Venkatesan , Kumar Abhishek , Shivashankar G. V.
Published: June 2013

Physical forces in the form of substrate rigidity or geometrical constraints have been shown to alter gene expression profile and differentiation programs. However, the underlying mechanism of gene regulation by these mechanical cues is largely unknown. In this work, we use micropatterned substrates to alter cellular geometry (shape, aspect ratio, and size) and study the nuclear mechanotransduction to regulate gene expression. Genome-wide transcriptome analysis revealed cell geometry-dependent alterations in actin-related gene expression. Increase in cell size reinforced expression of matrix-related genes, whereas reduced cell-substrate contact resulted in up-regulation of genes involved in cellular homeostasis. We also show that large-scale changes in gene-expression profile mapped onto differential modulation of nuclear morphology, actomyosin contractility and histone acetylation. Interestingly, cytoplasmic-to-nuclear redistribution of histone deacetylase 3 modulated histone acetylation in an actomyosin-dependent manner. In addition, we show that geometric constraints altered the nuclear fraction of myocardin-related transcription factor. These fractions exhibited hindered diffusion time scale within the nucleus, correlated with enhanced serum-response element promoter activity. Furthermore, nuclear accumulation of myocardin-related transcription factor also modulated NF-κB activity. Taken together, our work provides modularity in switching gene-expression patterns by cell geometric constraints via actomyosin contractility.
Caenorhabditis elegans
centriolar protein SAS-6 forms a spiral that is consistent with imparting a ninefold symmetry
Authors: Hilbert Manuel , Erat Michèle C. , Hachet Virginie , Guichard Paul , Blank Iris D. , Flückiger Isabelle , Slater Leanne , Lowe Edward D. , Hatzopoulos Georgios N. , Steinmetz Michel O. , Gönczy Pierre , Vakonakis Ioannis
Published: June 2013

Centrioles are evolutionary conserved organelles that give rise to cilia and flagella as well as centrosomes. Centrioles display a characteristic ninefold symmetry imposed by the spindle assembly abnormal protein 6 (SAS-6) family. SAS-6 from
Chlamydomonas reinhardtii
and
Danio rerio
was shown to form ninefold symmetric, ring-shaped oligomers in vitro that were similar to the cartwheels observed in vivo during early steps of centriole assembly in most species. Here, we report crystallographic and EM analyses showing that, instead,
Caenorhabotis elegans
SAS-6 self-assembles into a spiral arrangement. Remarkably, we find that this spiral arrangement is also consistent with ninefold symmetry, suggesting that two distinct SAS-6 oligomerization architectures can direct the same output symmetry. Sequence analysis suggests that SAS-6 spirals are restricted to specific nematodes. This oligomeric arrangement may provide a structural basis for the presence of a central tube instead of a cartwheel during centriole assembly in these species.
Vibrational imaging of newly synthesized proteins in live cells by stimulated Raman scattering microscopy
Authors: Wei Lu , Yu Yong , Shen Yihui , Wang Meng C. , Min Wei
Published: June 2013

Synthesis of new proteins, a key step in the central dogma of molecular biology, has been a major biological process by which cells respond rapidly to environmental cues in both physiological and pathological conditions. However, the selective visualization of a newly synthesized proteome in living systems with subcellular resolution has proven to be rather challenging, despite the extensive efforts along the lines of fluorescence staining, autoradiography, and mass spectrometry. Herein, we report an imaging technique to visualize nascent proteins by harnessing the emerging stimulated Raman scattering (SRS) microscopy coupled with metabolic incorporation of deuterium-labeled amino acids. As a first demonstration, we imaged newly synthesized proteins in live mammalian cells with high spatial–temporal resolution without fixation or staining. Subcellular compartments with fast protein turnover in HeLa and HEK293T cells, and newly grown neurites in differentiating neuron-like N2A cells, are clearly identified via this imaging technique. Technically, incorporation of deuterium-labeled amino acids is minimally perturbative to live cells, whereas SRS imaging of exogenous carbon–deuterium bonds (C–D) in the cell-silent Raman region is highly sensitive, specific, and compatible with living systems. Moreover, coupled with label-free SRS imaging of the total proteome, our method can readily generate spatial maps of the quantitative ratio between new and total proteomes. Thus, this technique of nonlinear vibrational imaging of stable isotope incorporation will be a valuable tool to advance our understanding of the complex spatial and temporal dynamics of newly synthesized proteome in vivo.
Molecular circuit involving KLK4 integrates androgen and mTOR signaling in prostate cancer
Authors: Jin Yang , Qu Su , Tesikova Martina , Wang Ling , Kristian Alexandr , Mælandsmo Gunhild M. , Kong Haiying , Zhang Tianzhou , Jerónimo Carmen , Teixeira Manuel R. , Yuca Erkan , Tekedereli Ibrahim , Gorgulu Kivanc , Alpay Neslihan , Sood Anil K. , Lopez-Berestein Gabriel , Danielsen Håvard E. , Ozpolat Bulent , Saatcioglu Fahri
Published: June 2013

Significance

All cancer lesions sustain alterations in signaling pathways, which are the drivers of disease initiation and progression. Study of altered signaling in cancer is thus important to develop more effective therapeutic regimens as well as better prognostic markers. In this study, we show that two of the most frequently altered signaling pathways in prostate cancer, the androgen receptor and the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin pathways, are dependent on kallikrein related peptidase 4 (KLK4), whose expression is highly prostate enriched. Our results suggest that KLK4 has a central role in prostate cancer survival and that KLK4 silencing may have significant therapeutic efficacy.
An exogenous retrovirus isolated from koalas with malignant neoplasias in a US zoo
Authors: Xu Wenqin , Stadler Cynthia K. , Gorman Kristen , Jensen Nathaniel , Kim David , Zheng HaoQiang , Tang Shaohua , Switzer William M. , Pye Geoffrey W. , Eiden Maribeth V.
Published: June 2013

Leukemia and lymphoma account for more than 60% of deaths in captive koalas (
Phascolarctos cinereus
) in northeastern Australia. Although the endogenizing gammaretrovirus koala endogenous retrovirus (KoRV) was isolated from these koalas, KoRV has not been definitively associated with leukemogenesis. We performed KoRV screening in koalas from the San Diego Zoo, maintained for more than 45 y with very limited outbreeding, and the Los Angeles Zoo, maintained by continuously assimilating captive-born Australian koalas. San Diego Zoo koalas are currently free of malignant neoplasias and were infected with only endogenous KoRV, which we now term subtype “KoRV-A,” whereas Los Angeles Zoo koalas with lymphomas/leukemias are infected in addition to KoRV-A by a unique KoRV we term subtype “KoRV-B.” KoRV-B is most divergent in the envelope protein and uses a host receptor distinct from KoRV-A. KoRV-B also has duplicated enhancer regions in the LTR associated with increased pathology in gammaretroviruses. Whereas KoRV-A uses the sodium-dependent phosphate transporter 1 (PiT1) as a receptor, KoRV-B employs a different receptor, the thiamine transporter 1 (THTR1), to infect cells. KoRV-B is transmitted from dam to offspring through de novo infection, rather than via genetic inheritance like KoRV-A. Detection of KoRV-B in native Australian koalas should provide a history, and a mode for remediation, of leukemia/lymphoma currently endemic in this population.
Ligands that interact with putative MOR-mGluR5 heteromer in mice with inflammatory pain produce potent antinociception
Authors: Akgün Eyup , Javed Muhammad I. , Lunzer Mary M. , Smeester Branden A. , Beitz Al J. , Portoghese Philip S.
Published: June 2013

The low effectiveness of morphine and related mu opioid analgesics for the treatment of chronic inflammatory pain is a result of opioid-induced release of proinflammatory cytokines and glutamate that lower the pain threshold. In this regard, the use of opioids with metabotropic glutamate-5 receptor (mGluR
5
) antagonist has been reported to increase the efficacy of morphine and prevent the establishment of adverse effects during chronic use. Given the presence of opioid receptors (MORs) and mGluR
5
in glia and neurons, together with reports that suggest coexpressed MOR/mGluR
5
receptors in cultured cells associate as a heteromer, the possibility that such a heteromer could be a target in vivo was addressed by the design and synthesis of a series of bivalent ligands that contain mu opioid agonist and mGluR
5
antagonist pharmacophores linked through spacers of varying length (10–24 atoms). The series was evaluated for antinociception using the tail-flick and von Frey assays in mice pretreated with lipopolysaccharide (LPS) or in mice with bone cancer. In LPS-pretreated mice, MMG22 (4c, 22-atom spacer) was the most potent member of the series (intrathecal ED
50
∼9 fmol per mouse), whereas in untreated mice its ED
50
was more than three orders of magnitude higher. As members of the series with shorter or longer spacers have ≥500-fold higher ED
50s
in LPS-treated mice, the exceptional potency of MMG22 may be a result of the optimal bridging of protomers in a putative MOR-mGluR
5
heteromer. The finding that MMG22 possesses a >10
6
therapeutic ratio suggests that it may be an excellent candidate for treatment of chronic, intractable pain via spinal administration.
Decorin causes autophagy in endothelial cells via Peg3
Authors: Buraschi Simone , Neill Thomas , Goyal Atul , Poluzzi Chiara , Smythies James , Owens Rick T. , Schaefer Liliana , Torres Annabel , Iozzo Renato V.
Published: June 2013

Significance

We identified a function for a member of the extracellular matrix in the regulation of autophagy. Decorin, a member of the small leucine-rich proteoglycan family and an established pan-receptor tyrosine kinase inhibitor, evokes endothelial cell autophagy and inhibits angiogenesis. This process is mediated by a high-affinity interaction with VEGFR2 which leads to increased levels of Peg3, a tumor-suppressor gene. We provide mechanistic evidence that Peg3 is required to maintain basal levels of Beclin 1, a major autophagic marker. These data provide a paradigmatic shift for other soluble matrix constituents to regulate autophagy.
Rasip1 mediates Rap1 regulation of Rho in endothelial barrier function through ArhGAP29
Authors: Post Anneke , Pannekoek Willem-Jan , Ross Sarah H. , Verlaan Ingrid , Brouwer Patricia M. , Bos Johannes L.
Published: June 2013

Rap1 is a small GTPase regulating cell–cell adhesion, cell–matrix adhesion, and actin rearrangements, all processes dynamically coordinated during cell spreading and endothelial barrier function. Here, we identify the adaptor protein ras-interacting protein 1 (Rasip1) as a Rap1-effector involved in cell spreading and endothelial barrier function. Using Förster resonance energy transfer, we show that Rasip1 interacts with active Rap1 in a cellular context. Rasip1 mediates Rap1-induced cell spreading through its interaction partner Rho GTPase-activating protein 29 (ArhGAP29), a GTPase activating protein for Rho proteins. Accordingly, the Rap1–Rasip1 complex induces cell spreading by inhibiting Rho signaling. The Rasip1–ArhGAP29 pathway also functions in Rap1-mediated regulation of endothelial junctions, which controls endothelial barrier function. In this process, Rasip1 cooperates with its close relative ras-association and dilute domain-containing protein (Radil) to inhibit Rho-mediated stress fiber formation and induces junctional tightening. These results reveal an effector pathway for Rap1 in the modulation of Rho signaling and actin dynamics, through which Rap1 modulates endothelial barrier function.
Patterning droplets with durotaxis
Authors: Style Robert W. , Che Yonglu , Park Su Ji , Weon Byung Mook , Je Jung Ho , Hyland Callen , German Guy K. , Power Michael P. , Wilen Larry A. , Wettlaufer John S. , Dufresne Eric R.
Published: June 2013

Numerous cell types have shown a remarkable ability to detect and move along gradients in stiffness of an underlying substrate—a process known as durotaxis. The mechanisms underlying durotaxis are still unresolved, but generally believed to involve active sensing and locomotion. Here, we show that simple liquid droplets also undergo durotaxis. By modulating substrate stiffness, we obtain fine control of droplet position on soft, flat substrates. Unlike other control mechanisms, droplet durotaxis works without imposing chemical, thermal, electrical, or topographical gradients. We show that droplet durotaxis can be used to create large-scale droplet patterns and is potentially useful for many applications, such as microfluidics, thermal control, and microfabrication.