bluuebunny/crossref_metadata_2025 huggingface dataset:
Mass-analyzed-threshold-ionization (MATI) spectroscopy of 1,2,3-substituted halogenated benzenes via different intermediate vibrational states in the S1 state
Authors: Krüger Sascha , Witte Frank , Helfrich Jan , Grotemeyer Jürgen
Published: November 2014

Non-planar geometrical distortion upon excitation (S1 ← S0) and replanarisation upon ionization (D0 ← S1) of some hetero-substituted halogenated benzenes.
A solvent additive to enhance the efficiency and the thermal stability of polymer:fullerene solar cells
Authors: Derue L. , Lecourtier C. , Gorisse T. , Hirsch L. , Dautel O. , Wantz G.
Published: November 2014

A novel bisazide molecule to be used in polymer–fullerene bulk heterojunction (BHJ) solar cells with two distinct functionalities is reported here.
Structural characterization of holo- and apo-myoglobin in the gas phase by ultraviolet photodissociation mass spectrometry
Authors: Cammarata Michael B. , Brodbelt Jennifer S.
Published: November 2014

193 nm UV photodissociation of myoglobin in the gas phase showed preferential backbone cleavages in regions with higher relativeB-factors.
Self-assembled three-dimensional hierarchical porous V2O5/graphene hybrid aerogels for supercapacitors with high energy density and long cycle life
Authors: Wu Yingjie , Gao Guohua , Wu Guangming
Published: November 2014

A self-assembled three-dimensional hierarchical porous V2O5/graphene hybrid aerogel for high-performance supercapacitor was synthesized.
Thermal stabilization of energetic materials by the aromatic nitrogen-rich 4,4′,5,5′-tetraamino-3,3′-bi-1,2,4-triazolium cation
Authors: Klapötke Thomas M. , Schmid Philipp. C. , Schnell Simon , Stierstorfer Jörg
Published: November 2014

Crystals of the highly energetic material 4,4′,5,5′-tetraamino-3,3′-bi-1,2,4-triazolium dinitramide (2). This compound is representative for the improvement of thermal stability resulting from the insertion of the long disregarded 4,4′,5,5′-tetraamino-3,3′-bi-1,2,4-triazolium cation.
The eukaryotic elongation factor eEF1A1 interacts with SAMHD1
Authors: Morrissey Catherine , Schwefel David , Ennis-Adeniran Valerie , Taylor Ian A. , Crow Yanick J. , Webb Michelle
Published: November 2014

Mutations in SAMHD1 cause Aicardi–Goutières syndrome (AGS), a Mendelian inflammatory disease which displays remarkable clinical and biochemical overlap with congenital viral infection. SAMHD1 (SAM domain and HD domain-containing protein 1) has also been defined as an HIV-1 restriction-factor that, through a novel triphosphohydrolase activity, inhibits early stage HIV-1 replication in myeloid-derived dendritic cells (MDDCs), macrophages and resting CD4+ T-cells. The potent activity of SAMHD1 is likely to be the subject of a variety of regulatory mechanisms. Knowledge of proteins that interact with SAMHD1 may not only enhance our understanding of the pathogenesis of AGS, but may also provide further details on the link between the regulation of cellular dNTPs and HIV-1 restriction. In the present study, we used a yeast two-hybrid screen and pull-down analysis followed by MS to identify the eukaryotic elongation factor 1A1 (eEF1A1) as a potential interaction partner of SAMHD1. This interaction was confirmed by unbiased co-immunoprecipitation and demonstrated in situ by a proximity ligation assay (PLA). We show that this interaction is enhanced in mutant SAMHD1 cell lines and suggest that eEF1A1 may mediate SAMHD1 turnover by targeting it to the proteosome for degradation through association with Cullin4A and Rbx1.
miR-98 delays skeletal muscle differentiation by down-regulating E2F5
Authors: Kropp Jeremie , Degerny Cindy , Morozova Nadezda , Pontis Julien , Harel-Bellan Annick , Polesskaya Anna
Published: November 2014

A genome-wide screen had previously shown that knocking down miR-98 and let-7g, two miRNAs of the let-7 family, leads to a dramatic increase in terminal myogenic differentiation. In the present paper, we report that a transcriptomic analysis of human myoblasts, where miR-98 was knocked down, revealed that approximately 240 genes were sensitive to miR-98 depletion. Among these potential targets of miR-98, we identified the transcriptional repressor E2F5 and showed that it is a direct target of miR-98. Knocking down simultaneously E2F5 and miR-98 almost fully restored normal differentiation, indicating that E2F5 is involved in the regulation of skeletal muscle differentiation. We subsequently show that E2F5 can bind to the promoters of two inhibitors of terminal muscle differentiation, ID1 (inhibitor of DNA binding 1) and HMOX1 (heme oxygenase 1), which decreases their expression in skeletal myoblasts. We conclude that miR-98 regulates muscle differentiation by altering the expression of the transcription factor E2F5 and, in turn, of multiple E2F5 targets.
Status of research toward the ITER disruption mitigation system
Authors: Hollmann E. M. , Aleynikov P. B. , Fülöp T. , Humphreys D. A. , Izzo V. A. , Lehnen M. , Lukash V. E. , Papp G. , Pautasso G. , Saint-Laurent F. , Snipes J. A.
Published: November 2014

An overview of the present status of research toward the final design of the ITER disruption mitigation system (DMS) is given. The ITER DMS is based on massive injection of impurities, in order to radiate the plasma stored energy and mitigate the potentially damaging effects of disruptions. The design of this system will be extremely challenging due to many physics and engineering constraints such as limitations on port access and the amount and species of injected impurities. Additionally, many physics questions relevant to the design of the ITER disruption mitigation system remain unsolved such as the mechanisms for mixing and assimilation of injected impurities during the rapid shutdown and the mechanisms for the subsequent formation and dissipation of runaway electron current.
A multiblob approach to colloidal hydrodynamics with inherent lubrication
Authors: Vázquez-Quesada Adolfo , Balboa Usabiaga Florencio , Delgado-Buscalioni Rafael
Published: November 2014

This work presents an intermediate resolution model of the hydrodynamics of colloidal particles based on a mixed Eulerian-Lagrangian formulation. The particle is constructed with a small set of overlapping Peskin's Immersed Boundary kernels (blobs) which are held together by springs to build up a particle impenetrable core. Here, we used 12 blobs placed in the vertexes of an icosahedron with an extra one in its center. Although the particle surface is not explicitly resolved, we show that the short-distance hydrodynamic responses (flow profiles, translational and rotational mobilities) agree with spherical colloids and provide consistent effective radii. A remarkable property of the present multiblob model is that it naturally provides zero relative mobility at some finite inter-particle distance. In terms of mutual friction, this divergent force accurately represents the “soft” lubrication regime of spherical colloids and permits to resolve the increase of the solution viscosity up to moderately dense systems with volume fraction up to about 0.50. This intermediate resolution model is able to recover highly non-trivial (many-body) hydrodynamics using small particles whose radii are similar to the grid size h (in the range [1.6 − 3.2] h). Considering that the cost of the embedding fluid phase scales such as the cube of the particle radius, this result brings about a significant computational speed-up. Our code Fluam works in Graphics Processor Units and uses Fast Fourier Transform for the Poisson solver, which further improves its efficiency.
A non-invasive acoustical method to measure the mean roughness height of the free surface of a turbulent shallow water flow
Authors: Krynkin A. , Horoshenkov K. V. , Nichols A. , Tait S. J.
Published: November 2014

In this paper, the directivity of the airborne sound field scattered by a dynamically rough free flow surface in a flume is used to determine the mean roughness height for six hydraulic conditions in which the uniform depth of the turbulent flow. The nonlinear curve fitting method is used to minimize the error between the predicted directivity and directivity data. The data fitting algorithm is based on the averaged solution for the scattered sound pressure as a function of angle which is derived through the Kirchhoff integral and its approximations. This solution takes into account the directivity of the acoustic source. For the adopted source and receiver geometry and acoustic frequency it is shown that the contribution from the stationary phase point (single specular point on the rough surface) yields similar results to those which can be obtained through the full Kirchhoff's integral. The accuracy in the inverted mean roughness height is comparable to that achieved with an array of conductive wave probes. This method enables non-invasive estimation of the flow Reynolds number and uniform flow depth.
Laser-driven localization of collective CO vibrations in metal-carbonyl complexes
Authors: Lisaj Mateusz , Kühn Oliver
Published: November 2014

Using the example of a cobalt dicarbonyl complex it is shown that two perpendicular linearly polarized IR laser pulses can be used to trigger an excitation of the delocalized CO stretching modes, which corresponds to an alternating localization of the vibration within one CO bond. The switching time for localization in either of the two bonds is determined by the energy gap between the symmetric and asymmetric fundamental transition frequencies. The phase of the oscillation between the two local bond excitations can be tuned by the relative phase of the two pulses. The extend of control of bond localization is limited by the anharmonicity of the potential energy surfaces leading to wave packet dispersion. This prevents such a simple pulse scheme from being used for laser-driven bond breaking in the considered example.
Synergistic cross-scale coupling of turbulence in a tokamak plasma
Authors: Howard N. T. , Holland C. , White A. E. , Greenwald M. , Candy J.
Published: November 2014

For the first time, nonlinear gyrokinetic simulations spanning both the ion and electron spatio-temporal scales have been performed with realistic electron mass ratio ((mD∕me)1∕2 = 60.0), realistic geometry, and all experimental inputs, demonstrating the coexistence and synergy of ion (kθρs∼O(1.0)) and electron-scale (kθρe∼O(1.0)) turbulence in the core of a tokamak plasma. All multi-scale simulations utilized the GYRO code [J. Candy and R. E. Waltz, J. Comput. Phys. 186, 545 (2003)] to study the coupling of ion and electron-scale turbulence in the core (r/a = 0.6) of an Alcator C-Mod L-mode discharge shown previously to exhibit an under-prediction of the electron heat flux when using simulations only including ion-scale turbulence. Electron-scale turbulence is found to play a dominant role in setting the electron heat flux level and radially elongated (kr ≪ kθ) “streamers” are found to coexist with ion-scale eddies in experimental plasma conditions. Inclusion of electron-scale turbulence in these simulations is found to increase both ion and electron heat flux levels by enhancing the transport at the ion-scale while also driving electron heat flux at sub-ρi scales. The combined increases in the low and high-k driven electron heat flux may explain previously observed discrepancies between simulated and experimental electron heat fluxes and indicates a complex interaction of short and long wavelength turbulence.
Ultrafast magnetization switching by spin-orbit torques
Authors: Garello Kevin , Avci Can Onur , Miron Ioan Mihai , Baumgartner Manuel , Ghosh Abhijit , Auffret Stéphane , Boulle Olivier , Gaudin Gilles , Gambardella Pietro
Published: November 2014

Spin-orbit torques induced by spin Hall and interfacial effects in heavy metal/ferromagnetic bilayers allow for a switching geometry based on in-plane current injection. Using this geometry, we demonstrate deterministic magnetization reversal by current pulses ranging from 180 ps to ms in Pt/Co/AlOx dots with lateral dimensions of 90 nm. We characterize the switching probability and critical current Ic as a function of pulse length, amplitude, and external field. Our data evidence two distinct regimes: a short-time intrinsic regime, where Ic scales linearly with the inverse of the pulse length, and a long-time thermally assisted regime, where Ic varies weakly. Both regimes are consistent with magnetization reversal proceeding by nucleation and fast propagation of domains. We find that Ic is a factor 3–4 smaller compared to a single domain model and that the incubation time is negligibly small, which is a hallmark feature of spin-orbit torques.
On-chip temperature-compensated Love mode surface acoustic wave device for gravimetric sensing
Authors: Liu Q. , Flewitt A. J.
Published: November 2014

Love mode surface acoustic wave (SAW) sensors have been recognized as one of the most sensitive devices for gravimetric sensors in liquid environments such as bio sensors. Device operation is based upon measuring changes in the transmitted (S21) frequency and phase of the first-order Love wave resonance associated with the device upon on attachment of mass. However, temperature variations also cause a change in the first order S21 parameters. In this work, shallow grooved reflectors and a “dotted” single phase unidirectional interdigitated transducer (D-SPUDT) have been added to the basic SAW structure, which promote unidirectional Love wave propagation from the device's input interdigitated transducers. Not only does this enhance the first-order S21 signal but also it allows propagation of a third-order Love wave. The attenuation coefficient of the third-order wave is sufficiently great that, whilst there is a clear reflected S11 signal, the third-order wave does not propagate into the gravimetric sensing area of the device. As a result, whilst the third-order S11 signal is affected by temperature changes, it is unaffected by mass attachment in the sensing area. It is shown that this signal can be used to remove temperature effects from the first-order S21 signal in real time. This allows gravimetric sensing to take place in an environment without the need for any other temperature measurement or temperature control; this is a particular requirement of gravimetric biosensors.
Fast characterization of gold nanorods ensemble by correlating its structure with optical extinction spectral features
Authors: Hu Z. J. , Hou S. , Ji Y. L. , Wen T. , Liu W. Q. , Zhang H. , Shi X. W. , Yan J. , Wu X. C.
Published: November 2014

Owing to unique size- and shape- dependent localized surface plasmon resonance (LSPR) of noble metal nanoparticles (NPs), the optical extinction spectroscopy method (OES) has received much attention to characterize the geometry of metal NPs by fitting experimental UV-vis-NIR spectra. In this work, we aimed to develop a more convenient and accurate OES method to characterize the structural parameters and concentration of the gold nanorods (GNRs) ensemble. The main difference between our approach and previous OES methods is that we solve this inverse spectra problem by establishing the LSPR relation equations of GNRs ensemble so that there is no need of UV-vis-NIR spectra fitting process. The aspect ratio (AR) and AR distribution can be directly retrieved from two of UV-vis-NIR spectral parameters (peak position and full width at half maximum) using the obtained relation equations. Furthermore, the relation equations are modified for applying to the more general GNRs samples by considering the plasmon shift due to the near distance dielectric sensitivity. Finally, instead of inductively coupled plasma mass spectrometry (ICP-MS) measurement, we provide a more facile measure of the mass-volume concentration which can be determined from the extinction value at 400 nm. By comparing with the experimental results, it shows that the retrieved results by the relation equations are reliable.
Medical leadership is the New Black: or is it?
Authors: Jorm Christine , Parker Malcolm
Published: November 2014

Considerable resources are being invested in healthcare leadership development programs and there is a new requirement for leadership teaching for Australian medical students. The new attention to medical leadership may be a reaction to loss of medical status and power. There is little evidence for return on investment from such programs. It is simply not clear what kind of leadership training is needed for collaborative work to improve healthcare nor what kind of organisational structures enable productive exercise of medical leadership skills. Caution is recommended. What is known about the topic? Considerable resources are being invested in healthcare leadership development programs and there is a new requirement to add leadership to the curricula for Australian medical students. What does this paper add? The lack of logic in calls for mass leadership training is explored. This may not only be a poor return on investment but also potentially reinforce medical attitudes that are unhelpful for modern healthcare. What are the implications for practitioners? A cautious approach to training large numbers of doctors and students is recommended.
A Green Approach for Copper-Free Sonogashira Reaction of Aryl Halides with Phenylacetylene in the Presence of Nano-Pd/Phosphorylated Silica (SDPP/Pd0)
Authors: Iranpoor Nasser , Firouzabadi Habib , Motevalli Somayeh , Rajabi Khashayar
Published: November 2014

Silicadiphenyl phosphinite (SDPP) is used as the solid support for the generation of nano SDPP/Pd(0) from PdII as pre-catalyst. This nano catalyst was used for the efficient copper-free Sonogashira reaction of aryl halides in PEG-200 as a solvent. The nano Pd(0) that can be used as pre-prepared or as in situ-generated catalyst exhibited excellent reactivity and stability in the Sonogashira cross-coupling reactions with different aryl iodides, bromides, and also chlorides. This heterogeneous catalyst can be easily recovered and reused in several runs. The use of PEG as solvent and K2CO3 as inorganic base together with the heterogeneous nature of the reaction can be considered as green conditions for this reaction.
Localisation and endocrine control of hyaluronan synthase (HAS) 2, HAS3 and CD44 expression in sheep granulosa cells
Authors: Chavoshinejad R. , Marei W. F. A. , Hartshorne G. M. , Fouladi-Nashta A. A.
Published: November 2014

The aim of the present study was to investigate the hormonal regulation of hyaluronan (HA) components in sheep granulosa cells. HA components are present in the reproductive tract and have a range of physical and signalling properties related to reproductive function in several species. First, abattoir-derived ovaries of sheep were used to determine the localisation of HA synthase (HAS) 1–3 and CD44 proteins in antral follicles. Staining for HAS1–3 and CD44 proteins was most intense in the granulosa layer. Accordingly, the expression of HAS2, HAS3 and CD44 mRNA was measured in cultured granulosa cells exposed to 0–50 ng mL–1 of 17β-oestradiol and different combinations of oestradiol, gonadotropins, insulin-like growth factor (IGF)-1 and insulin for 48–96 h (1 ng mL–1 FSH, 10 ng mL–1 insulin, 10 ng mL–1 IGF-1, 40 ng mL–1 E2 and 25 ng mL–1 LH.). mRNA expression was quantified by real-time polymerase chain reaction using a fold induction method. The results revealed that the hormones tested generally stimulated mRNA expression of the genes of interest in cultured granulosa cells. Specifically, oestradiol, when combined with IGF-1, insulin and FSH, stimulated HAS2 mRNA expression. Oestradiol and LH had synergistic effects in increasing HAS3 mRNA expression. In conclusion, we suggest that the hormones studied differentially regulate HAS2, HAS3 and CD44 in ovine granulosa cells in vitro. Further work is needed to address the signalling pathways involved.
Lessons learnt from the first Australian ‘pop-up' HIV testing site
Authors: Gale Marianne , Holden Jo , Kitchener Samara , Knight Vickie , McNulty Anna , Price Karen , Leeman Craig , Cunningham Philip , Hayen Andrew , MacInytre C. Raina
Published: November 2014

Lessons learnt from the first ‘pop-up’ HIV testing site in Australia suggest that highly visible testing activity was acceptable in the context of inner Sydney and that pop-up sites may be a useful adjunct to clinic-based models. Further evaluation of alternative testing models is needed to inform the scale up of HIV testing in Australia.
Risk and vulnerability of key populations to HIV infection in Iran; knowledge, attitude and practises of female sex workers, prison inmates and people who inject drugs
Authors: Khajehkazemi Razieh , Haghdoost AliAkbar , Navadeh Soodabeh , Setayesh Hamidreza , Sajadi Leily , Osooli Mehdi , Mostafavi Ehsan
Published: November 2014

Background
In this study data of three national surveys conducted among female sex workers (FSW), prison inmates and people who inject drugs (PWID) were presented and compared in relation to knowledge, attitude, and practises. Methods: The surveys were conducted in 2009 and 2010 and included 2546 PWID, 872 FSW and 5530 prison inmates. Knowledge, attitude and practises towards HIV were measured through similar questions for each category. Results: Over 90% of all participants had ever heard of HIV/AIDS, although only approximately half of them perceived themselves at risk of contracting HIV. More than 80% were able to correctly identify the ways of preventing the sexual transmission of HIV; while more than two-thirds did not use condom in their last sexual contact. Approximately 20% of prisoners and FSW had a history of injecting drugs. Among all participants who have injected drugs, prisoners had the highest unsafe injecting behaviour at the last injection (61%), followed by FSW (11%) and PWID (3%). Conclusions: Despite major efforts to control the HIV epidemic in Iran, the level of risk and vulnerability among prisoners, FSW and PWID is still high. The level of comprehensive knowledge about HIV/AIDS is relatively good; however, their risk perception of contracting HIV is low and high-risk behaviours are prevalent. Therefore, HIV prevention programs should be redesigned in a more comprehensive way to identify the best venues to reach the largest number of people at a higher risk of contracting HIV and decrease their risk overlaps and vulnerability factors.
Direct observation of prefreezing at the interface melt–solid in polymer crystallization
Authors: Löhmann Ann-Kristin , Henze Thomas , Thurn-Albrecht Thomas
Published: November 2014

Significance

The microscopic ordering process that a liquid undergoes during crystallization is often initiated at an interface to a solid. Different processes have been suggested by theory to occur at this interface. Of special interest is prefreezing—the formation of a thin crystalline layer at the interface already at temperatures above the melting temperature. Because of the difficult accessibility of the buried interface, experimental proof of crystallization by prefreezing has been elusive in molecular systems. We here present direct in situ observations of such a process in a polymeric model system. The results not only contribute to our fundamental understanding of crystallization but might also be useful for the preparation of well-ordered oriented thin films of crystalline organic materials.
Modeling local and cross-species neuron number variations in the cerebral cortex as arising from a common mechanism
Authors: Cahalane Diarmuid J. , Charvet Christine J. , Finlay Barbara L.
Published: November 2014

Significance

Despite great diversity across mammals in the number of cortical neurons and the cognitive functions they support, the fundamental process which populates the cerebral cortex with neurons changes only subtly from the smallest rodents to the largest primates. Understanding how the dynamics of neurogenesis can vary will help unravel how the genome molds normal and disrupted cortical development. We gathered data on the growing and mature cortex to build a computational model of neurogenesis. The model recapitulates how dynamics, known to vary across species and across the cortex, sculpt the basic landscape of the embryonic cortex. Features of the cortex long thought to be the result of special selection are revealed as the necessary product of a conserved mechanism.
Whole-cell, multicolor superresolution imaging using volumetric multifocus microscopy
Authors: Hajj Bassam , Wisniewski Jan , El Beheiry Mohamed , Chen Jiji , Revyakin Andrey , Wu Carl , Dahan Maxime
Published: November 2014

Significance

A major challenge in modern biological studies is in the determination of the 3D molecular architecture of cellular organelles. In recent years, much progress in nanoscale imaging has been made because of the advent of superresolution optical microscopy. However, many superresolution techniques are still limited to 2D acquisition. Here, we show a volumetric approach for superresolution imaging based on the simultaneous imaging of multiple sample planes using multifocal microscopy. The depth over which structures can be reconstructed reaches 4 µm, comparable with the thickness of many cellular organelles or even whole cells.
Recombinant HIV envelope trimer selects for quaternary-dependent antibodies targeting the trimer apex
Authors: Sok Devin , van Gils Marit J. , Pauthner Matthias , Julien Jean-Philippe , Saye-Francisco Karen L. , Hsueh Jessica , Briney Bryan , Lee Jeong Hyun , Le Khoa M. , Lee Peter S. , Hua Yuanzi , Seaman Michael S. , Moore John P. , Ward Andrew B. , Wilson Ian A. , Sanders Rogier W. , Burton Dennis R.
Published: November 2014

Significance

Despite the high antigenic diversity of the HIV envelope trimer (Env), broadly neutralizing antibodies (bnAbs) have identified conserved regions that serve as targets for vaccine design. One of these regions is located at the apex of Env and is expressed fully only in the context of the correctly folded trimer. This work describes the isolation of bnAbs that target this region using a recombinant native-like Env trimer as an affinity reagent to sort specific antibody-producing cells. Characterization of these antibodies reveals a highly diverse antibody response against the trimer apex and provides molecular information that will be useful in the design of immunogens to elicit bnAbs to this region of Env.
Distinct roles of the photosystem II protein PsbS and zeaxanthin in the regulation of light harvesting in plants revealed by fluorescence lifetime snapshots
Authors: Sylak-Glassman Emily J. , Malnoë Alizée , De Re Eleonora , Brooks Matthew D. , Fischer Alexandra Lee , Niyogi Krishna K. , Fleming Graham R.
Published: November 2014

Significance

By comparing the form of the chlorophyll fluorescence decays in wild-type,
npq1
,
npq4
, and
npq1 npq4
plants, we show that the presence of violaxanthin deepoxidase (VDE), but not the protein PsbS, changes the excited-state relaxation dynamics of chlorophyll. PsbS has the strongest effect during the initial induction of quenching. The presence of both zeaxanthin and PsbS is required for strong quenching. This fluorescence lifetime technique helps elucidate both the kinetics with which quenching turns on and off and the relaxation dynamics of excited-state chlorophyll.
Mitochondrial serine protease HTRA2 p.G399S in a kindred with essential tremor and Parkinson disease
Authors: Unal Gulsuner Hilal , Gulsuner Suleyman , Mercan Fatma Nazli , Onat Onur Emre , Walsh Tom , Shahin Hashem , Lee Ming K. , Dogu Okan , Kansu Tulay , Topaloglu Haluk , Elibol Bulent , Akbostanci Cenk , King Mary-Claire , Ozcelik Tayfun , Tekinay Ayse B.
Published: November 2014

Significance

Essential tremor is one of the most frequent movement disorders of humans, but its causes remain largely unknown. In a six-generation family with both essential tremor and Parkinson disease, we identified a rare missense mutation ofHTRA2as the causative allele. Family members homozygous for this allele were more severely affected than those heterozygous for this allele. The same mutation had been associated with Parkinson characteristics in mouse mutants and with Parkinson disease in some, but not all, epidemiologic studies. Our results suggest thatHTRA2may be responsible for essential tremor in some families and that homozygosity for damaging alleles ofHTRA2may be responsible for Parkinson disease.
Deficiencies in tRNA synthetase editing activity cause cardioproteinopathy
Authors: Liu Ye , Satz Jakob S. , Vo My-Nuong , Nangle Leslie A. , Schimmel Paul , Ackerman Susan L.
Published: November 2014

Significance

Misfolded proteins are a hallmark of diverse human cardiac disorders including desmin-related cardiomyopathy and systemic amyloidosis. Defects in translational fidelity can cause neurodegeneration, however the consequences of mistranslation in other tissues, including the heart, are unknown. The fidelity of protein synthesis is largely ensured by aminoacyl-tRNA synthetases, and many tRNA synthetases contain editing domains that hydrolyze mischarged tRNAs, preventing incorporation of incorrect amino acids into proteins. Here, we show that diminished editing efficacy of the alanyl-tRNA synthetase causes misfolded protein aggregation and cell death in the mammalian heart. These results illuminate the importance of translational fidelity in cardiac homeostasis and suggest that genetic factors that disrupt the accuracy of translation may contribute to proteinopathies of the heart and other tissues.
Wnts produced by Osterix-expressing osteolineage cells regulate their proliferation and differentiation
Authors: Tan Si Hui , Senarath-Yapa Kshemendra , Chung Michael T. , Longaker Michael T. , Wu Joy Y. , Nusse Roeland
Published: November 2014

Significance

Despite the importance of Wnt signaling in bone biology, there is a knowledge gap in the identity of the cells that produce the Wnt ligands and the functions of Wnts produced by specific cell types. In our study, we comprehensively characterized the expression patterns of all 19 Wnts in the developing mouse bone by in situ hybridization, and further showed that Osterix-expressing cells can produce Wnts and respond to Wnt signaling. Additionally, we found that Wnts produced by these Osterix-expressing cells regulate their differentiation and proliferation. Through providing a better understanding of how Wnt signaling contributes to bone biology, our findings also have clinical implications for the mechanism of the osteoporotic drug that targets Sclerostin, a Wnt signaling antagonist.
Conventionalism, Truth, and Cosmological Furniture
Authors: Wisdom J. O.
Published: November 2014

The problem to be discussed here concerns ontology so far as it may not be formed by scientific theory. In brief terms, the problem arises in the following way. On the one hand, the world surely consists of whatever is there, irrespective of whether human beings are around or not, and irrespective especially of whether human beings have constructed any scientific theories depicting the nature of the world; on the other hand, scientific theories are subject to the limitation that we can never verify them or prove them to be true, so that the ontology prescribed by scientific theory is not firmly established but is only what is attributed to the world by a fallible scientific theory at any given time. The problem could also be put in terms of ‘conceptual networks’ or in terms of language-systems.
Racist Acts and Racist Humor
Authors: Philips Michael
Published: November 2014

Racist jokes are often funny. And part of this has to do with their racism. Many Polish jokes, for example, may easily be converted into moron jokes but are not at all funny when delivered as such. Consider two answers to ‘What has an I.Q. of 1007’: (a) a nation of morons; or (b) Poland. Similarly, jokes portraying Jews as cheap, Italians as cowards, and Greeks as dishonest may be told as jokes about how skinflints, cowards, or dishonest people get on in the world. But they are less funny as such (at least if one is not Jewish, Greek, or Italian). As this suggests, racist humor is ‘put down’ humor. We laugh, in part, because we find put-downs funny, sometimes even if they are about us. In many contexts, this tendency is relatively harmless; indeed, within reason, it may be therapeutic to join others in a good laugh at oneself. Why, then, all the commotion about racist humor?
A Review on Attachment and Adolescent Substance Abuse: Empirical Evidence and Implications for Prevention and Treatment
Authors: Schindler Andreas , Bröning Sonja
Published: November 2014

Background

This paper reviews research on the relation of attachment and substance use disorders (SUD) in adolescence. Based on a theoretical introduction, we review evidence for a possible general link between SUD and insecure attachment, for links between specific forms of SUD and specific patterns of attachment, and for studies on family patterns of attachment in adolescence.

Methods

Using medical and psychological databases, we identified 10 studies on adolescent SUD and another 13 studies on adult SUD.

Results

Empirical evidence strongly supports the assumption of insecure attachment in SUD samples. With regard to specific patterns of attachment, results mainly point towards fearful and dismissing-avoidance, whereas single studies report preoccupied and unresolved patterns. Results indicate different patterns of attachment in different groups of substance abusers, that is, fearful-avoidant attachment in heroin addicts and more heterogeneous results in abusers of other substances. Explorative data suggest different types of insecure family attachment patterns, which might imply different functions of substance abuse and lead to different treatment recommendations. Methodological problems such as poor assessment of SUD and the use of different measures of attachment limit comparability.

Conclusions

Although a lot of research is still needed to address the unknowns in the relation between attachment and SUD, there is strong evidence for a general link between SUD and insecure attachment. Data on connections between different patterns of attachment and different pathways towards SUD are less conclusive but mainly point to disorganized and externalizing pathways. Evidence suggests that fostering attachment security might improve the outcome of state-of-the-art approaches in both early interventional treatment and prevention. Implications for individual and family approaches are outlined.
Potential role of orexin and sleep modulation in the pathogenesis of Alzheimer’s disease
Authors: Roh Jee Hoon , Jiang Hong , Finn Mary Beth , Stewart Floy R. , Mahan Thomas E. , Cirrito John R. , Heda Ashish , Snider B. Joy , Li Mingjie , Yanagisawa Masashi , de Lecea Luis , Holtzman David M.
Published: November 2014

Age-related aggregation of amyloid-β (Aβ) is an upstream pathological event in Alzheimer’s disease (AD) pathogenesis, and it disrupts the sleep–wake cycle. The amount of sleep declines with aging and to a greater extent in AD. Poor sleep quality and insufficient amounts of sleep have been noted in humans with preclinical evidence of AD. However, how the amount and quality of sleep affects Aβ aggregation is not yet well understood. Orexins (hypocretins) initiate and maintain wakefulness, and loss of orexin-producing neurons causes narcolepsy. We tried to determine whether orexin release or secondary changes in sleep via orexin modulation affect Aβ pathology. Amyloid precursor protein (APP)/Presenilin 1 (PS1) transgenic mice, in which the orexin gene is knocked out, showed a marked decrease in the amount of Aβ pathology in the brain with an increase in sleep time. Focal overexpression of orexin in the hippocampus in APP/PS1 mice did not alter the total amount of sleep/wakefulness and the amount of Aβ pathology. In contrast, sleep deprivation or increasing wakefulness by rescue of orexinergic neurons in APP/PS1 mice lacking orexin increased the amount of Aβ pathology in the brain. Collectively, modulation of orexin and its effects on sleep appear to modulate Aβ pathology in the brain.
Multilevel Research Strategies and Biological Systems
Authors: O’Malley Maureen A. , Brigandt Ingo , Love Alan C. , Crawford John W. , Gilbert Jack A. , Knight Rob , Mitchell Sandra D. , Rohwer Forest
Published: November 2014

Multilevel research strategies characterize contemporary molecular inquiry into biological systems. We outline conceptual, methodological, and explanatory dimensions of these multilevel strategies in microbial ecology, systems biology, protein research, and developmental biology. This review of emerging lines of inquiry in these fields suggests that multilevel research in molecular life sciences has significant implications for philosophical understandings of explanation, modeling, and representation.
Strict interior approximation of sets of finite perimeter and functions of bounded variation
Authors: Schmidt Thomas
Published: November 2014

It is well known that sets of finite perimeter can be strictly approximated by smooth sets, while, in general, one cannot hope to approximate anopensetΩ\Omegaof finite perimeter inRn\mathbb {R}^nstrictlyfrom within. In this note we show that, nevertheless, the latter type of approximation is possible under the mild hypothesis that the(n−1)(n{-}1)-dimensional Hausdorff measure of the topological boundary∂Ω\partial \Omegaequals the perimeter ofΩ\Omega. We also discuss an optimality property of this hypothesis, and we establish a corresponding result on strict approximation ofBVBV-functions from a prescribed Dirichlet class.
A Birth‐Death Markov Chain Monte Carlo Method to Estimate the Number of States in a State‐Contingent Production Frontier Model
Authors: Arreola José Luis Preciado , Johnson Andrew L.
Published: November 2014

In this article we estimate a state‐contingent production frontier for a group of farms while endogenously estimating the number of states of nature induced by unobserved environmental variables. This estimation is conducted by using a birth‐death Markov chain Monte Carlo method. State‐contingent output is estimated conditioned on an observed input vector and an a priori unknown number of unobserved states, each of which is modeled as a component of a mixture of Gaussian distributions. In a panel data application, state‐independent dummy variables are used to control for time effects. The model is applied to 44 rice farms in the Philippines operating between 1990 and 1997. The endogenous estimation procedure indicates a unimodal posterior probability distribution on the number of states, with a median of three states. The estimated posterior coefficient values and their economic implications are compared to those of previous research that had assumed a fixed number of states determined exogenously. Goodness‐of‐fit testing is performed for the first time for a state‐contingent production model. The results indicate satisfactory fit and also provide insights regarding the degree of estimation error reduction achieved by utilizing a distribution for the number of states instead of a point estimate. All of our models show significant improvement in terms of mean squared error of in‐sample predictions against previous work. This application also demonstrates that using a state‐independent dummy time trend instead of a state‐contingent linear time trend leads to slightly smaller differences in state mean output levels, although input elasticities remain state‐contingent.
Expenditure Response to Increases in In‐Kind Transfers: Evidence from the Supplemental Nutrition Assistance Program
Authors: Beatty Timothy K.M. , Tuttle Charlotte J.
Published: November 2014

Economic theory predicts that households who receive less in Supplemental Nutrition Assistance Program benefits than they spend on food will treat SNAP benefits as if they were cash. However, empirical tests of these predictions draw different conclusions. In this study, we reexamine this question using recent increases in Supplemental Nutrition Assistance Program benefits, the largest of which was due to the American Recovery and Reinvestment Act of 2009. We find that increases in benefits cause households to increase their food budget share by more than would be predicted by theory. Results are robust to a host of specification tests.
Efficient searching and annotation of metabolic networks using chemical similarity
Authors: Pertusi Dante A. , Stine Andrew E. , Broadbelt Linda J. , Tyo Keith E.J.
Published: November 2014

Motivation: The urgent need for efficient and sustainable biological production of fuels and high-value chemicals has elicited a wave of in silico techniques for identifying promising novel pathways to these compounds in large putative metabolic networks. To date, these approaches have primarily used general graph search algorithms, which are prohibitively slow as putative metabolic networks may exceed 1 million compounds. To alleviate this limitation, we report two methods—SimIndex (SI) and SimZyme—which use chemical similarity of 2D chemical fingerprints to efficiently navigate large metabolic networks and propose enzymatic connections between the constituent nodes. We also report a Byers–Waterman type pathway search algorithm for further paring down pertinent networks.

Results: Benchmarking tests run with SI show it can reduce the number of nodes visited in searching a putative network by 100-fold with a computational time improvement of up to 105-fold. Subsequent Byers–Waterman search application further reduces the number of nodes searched by up to 100-fold, while SimZyme demonstrates ∼90% accuracy in matching query substrates with enzymes. Using these modules, we have designed and annotated an alternative to the methylerythritol phosphate pathway to produce isopentenyl pyrophosphate with more favorable thermodynamics than the native pathway. These algorithms will have a significant impact on our ability to use large metabolic networks that lack annotation of promiscuous reactions.

Availability and implementation: Python files will be available for download at http://tyolab.northwestern.edu/tools/.

Contact: k-tyo@northwestern.edu

Supplementary information: Supplementary data are available at Bioinformatics online.
genomation: a toolkit to summarize, annotate and visualize genomic intervals
Authors: Akalin Altuna , Franke Vedran , Vlahoviček Kristian , Mason Christopher E. , Schübeler Dirk
Published: November 2014

Summary: Biological insights can be obtained through computational integration of genomics data sets consisting of diverse types of information. The integration is often hampered by a large variety of existing file formats, often containing similar information, and the necessity to use complicated tools to achieve the desired results. We have built an R package, genomation, to expedite the extraction of biological information from high throughput data. The package works with a variety of genomic interval file types and enables easy summarization and annotation of high throughput data sets with given genomic annotations.

Availability and implementation: The software is currently distributed under MIT artistic license and freely available at http://bioinformatics.mdc-berlin.de/genomation, and through the Bioconductor framework.

Contact:  dirk.schubeler@fmi.ch, chm2042@med.cornell.edu, altuna.akalin@fmi.ch, or aakalin@gmail.com
QuasR: quantification and annotation of short reads in R
Authors: Gaidatzis Dimos , Lerch Anita , Hahne Florian , Stadler Michael B.
Published: November 2014

Summary: QuasR is a package for the integrated analysis of high-throughput sequencing data in R, covering all steps from read preprocessing, alignment and quality control to quantification. QuasR supports different experiment types (including RNA-seq, ChIP-seq and Bis-seq) and analysis variants (e.g. paired-end, stranded, spliced and allele-specific), and is integrated in Bioconductor so that its output can be directly processed for statistical analysis and visualization.

Availability and implementation: QuasR is implemented in R and C/C++. Source code and binaries for major platforms (Linux, OS X and MS Windows) are available from Bioconductor (www.bioconductor.org/packages/release/bioc/html/QuasR.html). The package includes a ‘vignette’ with step-by-step examples for typical work ﬂows.

Contact:  michael.stadler@fmi.ch

Supplementary information:  Supplementary data are available at Bioinformatics online.
The non-thermal superbubble in IC 10: the generation of cosmic ray electrons caught in the act
Authors: Heesen Volker , Brinks Elias , Krause Martin G. H. , Harwood Jeremy J. , Rau Urvashi , Rupen Michael P. , Hunter Deidre A. , Chyży Krzysztof T. , Kitchener Ged
Published: November 2014

Superbubbles are crucial for stellar feedback, with supposedly high (of the order of 10 per cent) thermalization rates. We combined multiband radio continuum observations from the Very Large Array (VLA) with Effelsberg data to study the non-thermal superbubble (NSB) in IC 10, a starburst dwarf irregular galaxy in the Local Group. Thermal emission was subtracted using a combination of Balmer Hα and VLA 32 GHz continuum maps. The bubble's non-thermal spectrum between 1.5 and 8.8 GHz displays curvature and can be well fitted with a standard model of an ageing cosmic ray electron population. With a derived equipartition magnetic field strength of 44 ± 8 μG, and measuring the radiation energy density from Spitzer MIPS maps as 5 ± 1 × 10−11 erg cm−3, we determine, based on the spectral curvature, a spectral age of the bubble of 1.0 ± 0.3 Myr. Analysis of the LITTLE THINGS H i data cube shows an expanding H i hole with 100 pc diameter and a dynamical age 3.8 ± 0.3 Myr, centred to within 16 pc on IC 10 X-1, a massive stellar mass black hole (M > 23 M⊙). The results are consistent with the expected evolution for a superbubble with a few massive stars, where a very energetic event like a Type Ic supernova/hypernova has taken place about 1 Myr ago. We discuss alternatives to this interpretation.
Waves in Ship Prices and Investment
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Authors: Greenwood Robin , Hanson Samuel G.
Published: November 2014

We study the link between investment boom and bust cycles and returns on capital in the dry bulk shipping industry. We show that high current ship earnings are associated with high used ship prices and heightened industry investment in new ships, but forecast low future returns. We propose and estimate a behavioral model of industry cycles that can account for the evidence. In our model, firms overextrapolate exogenous demand shocks and partially neglect the endogenous investment response of their competitors. As a result, firms overpay for ships and overinvest in booms and are disappointed by the subsequent low returns. Formal estimation of the model suggests that modest expectational errors can result in dramatic excess volatility in prices and investment.
Brachypodium distachyon–Cochliobolus sativus Pathosystem is a New Model for Studying Plant–Fungal Interactions in Cereal Crops
Authors: Zhong Shaobin , Ali Shaukat , Leng Yueqiang , Wang Rui , Garvin David F.
Published: November 2014

Cochliobolus sativus (anamorph: Bipolaris sorokiniana) causes spot blotch, common root rot, and kernel blight or black point in barley and wheat. However, little is known about the molecular mechanisms underlying the pathogenicity of C. sativus or the molecular basis of resistance and susceptibility in the hosts. This study aims to establish the model grass Brachypodium distachyon as a new model for studying plant–fungus interactions in cereal crops. Six B. distachyon lines were inoculated with five C. sativus isolates. The results indicated that all six B. distachyon lines were infected by the C. sativus isolates, with their levels of resistance varying depending on the fungal isolates used. Responses ranging from hypersensitive response-mediated resistance to complete susceptibility were observed in a large collection of B. distachyon (2n = 2x = 10) and B. hybridum (2n = 4x = 30) accessions inoculated with four of the C. sativus isolates. Evaluation of an F2 population derived from the cross between two of the B. distachyon lines, Bd1-1 and Bd3-1, with isolate Cs07-47-1 showed quantitative and transgressive segregation for resistance to C. sativus, suggesting that the resistance may be governed by quantitative trait loci from both parents. The availability of whole-genome sequences of both the host (B. distachyon) and the pathogen (C. sativus) makes this pathosystem an attractive model for studying this important disease of cereal crops.