bluuebunny/crossref_metadata_2025 huggingface dataset:
Abgrenzungskonzeption zur Definition Landarzt
Authors: Marschner C. , Wasem J. , Heymann R.
Published: July 2016

Vor dem Hintergrund der wissenschaftlichen Diskussion im Rahmen der Versorgungsforschung mangelt es nach wie vor an einer konkreten und einheitlichen Landarztdefinition. Diese wäre aber für die zukünftige Gestaltung der medizinischen Versorgungsstruktur in Deutschland dringend notwendig. Insbesondere die anhaltenden Diskussionen über den prognostizierten und bereits in Teilen Deutschlands gegenwärtigen Ärztemangel in ländlichen, zumeist strukturschwachen Regionen, stützen die Forderung nach einer Präzisierung des Landarztbegriffs. Nur auf Basis einer einheitlichen Definition erscheint es möglich, effiziente Lösungen regionsübergreifend entwickeln, diskutieren und zielgerichtet einsetzen zu können. Die Vielzahl bereits existierender Lösungsansätze wie z. B. die Telemedizin, Gesundheitszentren, Gemeindeschwestern, Übernahme ambulanter Versorgungsleistungen durch Krankenhäuser, Nachwuchsförderung usw., müssen evaluiert und dem tatsächlichen Bedarf entsprechend angepasst werden. Der zugrunde liegende Artikel stellt einen neu entwickelten Stufenplan zur Differenzierung zwischen Land- und Stadtärzten vor, welcher die Definition „Landarzt“ regionsadaptiert ermöglicht. Unter zur Hilfenahme der Definition kann dann eine Überprüfung und Weiterentwicklung der zuvor genannten Lösungsansätze stattfinden. Darüber hinaus besteht durch die Anwendung der Abgrenzungskonzeption die Chance, völlig neue Ideen und Lösungen im Rahmen der Versorgungsforschung zu kreieren. Die Grundlage der neuen Konzeption zur Land- und Stadtarztabgrenzung besteht im Wesentlichen aus den Abgrenzungsschritten: Grundzentrum (Schritt I), ländliche Besiedelung (Schritt II) sowie räumlich zentrale Lage (Schritt III). Diese 3 aufeinander aufbauenden Abgrenzungsschritte werden im Folgenden zunächst einzeln theoretisch hergeleitet. Im Anschluss erfolgt die praktische Anwendung der vorgestellten Konzeption an der Beispielregion Westfalen/Lippe. Das entwickelte Modell bietet zusammenfassend eine standardisierte Vorgehensweise, die unter zeitlichen und finanziellen Aspekten als realisierbar gilt. Ziel des vorliegenden Papiers ist vor allem ein Beitrag zur anhaltenden Diskussion der ambulanten Versorgungsforschung und insbesondere der Definition Landarzt zu leisten, die mit Hilfe des hier vorgestellten Modellansatzes auch Vergleiche zwischen verschiedenen Regionen Deutschlands ermöglicht.
Temperature gradient scale length measurement: A high accuracy application of electron cyclotron emission without calibration
Authors: Houshmandyar S. , Yang Z. J. , Phillips P. E. , Rowan W. L. , Hubbard A. E. , Rice J. E. , Hughes J. W. , Wolfe S. M.
Published: July 2016

Calibration is a crucial procedure in electron temperature (Te) inference from a typical electron cyclotron emission (ECE) diagnostic on tokamaks. Although the calibration provides an important multiplying factor for an individual ECE channel, the parameter ΔTe/Te is independent of any calibration. Since an ECE channel measures the cyclotron emission for a particular flux surface, a non-perturbing change in toroidal magnetic field changes the view of that channel. Hence the calibration-free parameter is a measure of Te gradient. BT-jog technique is presented here which employs the parameter and the raw ECE signals for direct measurement of electron temperature gradient scale length.
Composition dependence of the glass forming ability in binary mixtures: The role of demixing entropy
Authors: Nandi Ujjwal Kumar , Banerjee Atreyee , Chakrabarty Suman , Bhattacharyya Sarika Maitra
Published: July 2016

We present a comparative study of the glass forming ability of binary systems with varying composition, where the systems have similar global crystalline structure (CsCl+fcc). Biased Monte Carlo simulations using umbrella sampling technique show that the free energy cost to create a CsCl nucleus increases as the composition of the smaller particles is decreased. We find that systems with comparatively lower free energy cost to form CsCl nucleus exhibit more pronounced pre-crystalline demixing near the liquid/crystal interface. The structural frustration between the CsCl and fcc crystal demands this demixing. We show that closer to the equimolar mixture, the entropic penalty for demixing is lower and a glass forming system may crystallize when seeded with a nucleus. This entropic penalty as a function of composition shows a non-monotonic behaviour with a maximum at a composition similar to the well known Kob-Anderson (KA) model. Although the KA model shows the maximum entropic penalty and thus maximum frustration against CsCl formation, it also shows a strong tendency towards crystallization into fcc lattice of the larger “A” particles which can be explained from the study of the energetics. Thus for systems closer to the equimolar mixture although it is the requirement of demixing which provides their stability against crystallization, for KA model it is not demixing but slow dynamics and the presence of the “B” particles make it a good glass former. The locally favoured structure around “B” particles is quite similar to the CsCl structure and the incompatibility of CsCl and fcc hinders the fcc structure growth in the KA model. Although the glass forming binary systems studied here are quite similar, differing only in composition, we find that their glass forming ability cannot be attributed to a single phenomenon.
Full particle orbit effects in regular and stochastic magnetic fields
Authors: Ogawa Shun , Cambon Benjamin , Leoncini Xavier , Vittot Michel , del Castillo-Negrete Diego , Dif-Pradalier Guilhem , Garbet Xavier
Published: July 2016

We present a numerical study of charged particle motion in a time-independent magnetic field in cylindrical geometry. The magnetic field model consists of an unperturbed reversed-shear (non-monotonic q-profile) helical part and a perturbation consisting of a superposition of modes. Contrary to most of the previous studies, the particle trajectories are computed by directly solving the full Lorentz force equations of motion in a six-dimensional phase space using a sixth-order, implicit, symplectic Gauss-Legendre method. The level of stochasticity in the particle orbits is diagnosed using averaged, effective Poincare sections. It is shown that when only one mode is present, the particle orbits can be stochastic even though the magnetic field line orbits are not stochastic (i.e., fully integrable). The lack of integrability of the particle orbits in this case is related to separatrix crossing and the breakdown of the global conservation of the magnetic moment. Some perturbation consisting of two modes creates resonance overlapping, leading to Hamiltonian chaos in magnetic field lines. Then, the particle orbits exhibit a nontrivial dynamics depending on their energy and pitch angle. It is shown that the regions where the particle motion is stochastic decrease as the energy increases. The non-monotonicity of the q-profile implies the existence of magnetic ITBs (internal transport barriers) which correspond to shearless flux surfaces located in the vicinity of the q-profile minimum. It is shown that depending on the energy, these magnetic ITBs might or might not confine particles. That is, magnetic ITBs act as an energy-dependent particle confinement filter. Magnetic field lines in reversed-shear configurations exhibit topological bifurcations (from homoclinic to heteroclinic) due to separatrix reconnection. We show that a similar but more complex scenario appears in the case of particle orbits that depend in a non-trivial way on the energy and pitch angle of the particles.
Towards a pair natural orbital coupled cluster method for excited states
Authors: Dutta Achintya Kumar , Neese Frank , Izsák Róbert
Published: July 2016

The use of back-transformed pair natural orbitals in the calculation of excited state energies, ionization potentials, and electron affinities is investigated within the framework of equation of motion coupled cluster theory and its similarity transformed variant. Possible approaches to a more optimal use of pair natural orbitals in these methods are indicated.
Influence of laser induced hot electrons on the threshold for shock ignition of fusion reactions
Authors: Colaïtis A. , Ribeyre X. , Le Bel E. , Duchateau G. , Nicolaï Ph. , Tikhonchuk V.
Published: July 2016

The effects of Hot Electrons (HEs) generated by the nonlinear Laser-Plasma Interaction (LPI) on the dynamics of Shock Ignition Inertial Confinement Fusion targets are investigated. The coupling between the laser beam, plasma dynamics and hot electron generation and propagation is described with a radiative hydrodynamics code using an inline model based on Paraxial Complex Geometrical Optics [Colaïtis et al., Phys. Rev. E 92, 041101 (2015)]. Two targets are considered: the pure-DT HiPER target and a CH-DT design with baseline spike powers of the order of 200–300 TW. In both cases, accounting for the LPI-generated HEs leads to non-igniting targets when using the baseline spike powers. While HEs are found to increase the ignitor shock pressure, they also preheat the bulk of the imploding shell, notably causing its expansion and contamination of the hotspot with the dense shell material before the time of shock convergence. The associated increase in hotspot mass (i) increases the ignitor shock pressure required to ignite the fusion reactions and (ii) significantly increases the power losses through Bremsstrahlung X-ray radiation, thus rapidly cooling the hotspot. These effects are less prominent for the CH-DT target where the plastic ablator shields the lower energy LPI-HE spectrum. Simulations using higher laser spike powers of 500 TW suggest that the CH-DT capsule marginally ignites, with an ignition window width significantly smaller than without LPI-HEs, and with three quarters of the baseline target yield. The latter effect arises from the relation between the shock launching time and the shell areal density, which becomes relevant in presence of a LPI-HE preheating.
Accurate Young’s modulus measurement based on Rayleigh wave velocity and empirical Poisson’s ratio
Authors: Li Mingxia , Feng Zhihua
Published: July 2016

This paper presents a method for Young’s modulus measurement based on Rayleigh wave speed. The error in Poisson’s ratio has weak influence on the measurement of Young’s modulus based on Rayleigh wave speed, and Poisson’s ratio minimally varies in a certain material; thus, we can accurately estimate Young’s modulus with surface wave speed and a rough Poisson’s ratio. We numerically analysed three methods using Rayleigh, longitudinal, and transversal wave speed, respectively, and the error in Poisson’s ratio shows the least influence on the result in the method involving Rayleigh wave speed. An experiment was performed and has proved the feasibility of this method. Device for speed measuring could be small, and no sample pretreatment is needed. Hence, developing a portable instrument based on this method is possible. This method makes a good compromise between usability and precision.
Formation of nanosized monolayer MoS2 by oxygen-assisted thinning of multilayer MoS2
Authors: Neupane Guru P. , Dhakal Krishna P. , Kim Hyun , Lee Jubok , Kim Min Su , Han Ganghee , Lee Young Hee , Kim Jeongyong
Published: July 2016

We report the controllable nanosized local thinning of multi-layer (2 L and 3 L)-thickness MoS2 films down to the monolayer (1 L) thickness using the simple method of annealing in a dry oxygen atmosphere. The annealing temperature was optimized in the range of 240 °C to 270 °C for 1.5 h, and 1 L thick nanosized pits were developed on the uniform film of the 2 L and 3 L MoS2 grown using the chemical vapor deposition method. We characterized the formation of the 1 L nanosized pits using nanoscale confocal photoluminescence (PL) and Raman spectroscopy. We observed that the PL intensity increased and the Raman frequency shifted, representative of the characteristics of 1 L MoS2 films. A subsequent hydrogen treatment process was useful for removing the oxygen-induced doping effect resulting from the annealing.
Fractional-dimensional Child-Langmuir law for a rough cathode
Authors: Zubair M. , Ang L. K.
Published: July 2016

This work presents a self-consistent model of space charge limited current transport in a gap combined of free-space and fractional-dimensional space (Fα), where α is the fractional dimension in the range 0 < α ≤ 1. In this approach, a closed-form fractional-dimensional generalization of Child-Langmuir (CL) law is derived in classical regime which is then used to model the effect of cathode surface roughness in a vacuum diode by replacing the rough cathode with a smooth cathode placed in a layer of effective fractional-dimensional space. Smooth transition of CL law from the fractional-dimensional to integer-dimensional space is also demonstrated. The model has been validated by comparing results with an experiment.
Strong perpendicular exchange bias in epitaxial La0.7Sr0.3MnO3:LaFeO3 nanocomposite thin films
Authors: Fan Meng , Zhang Wenrui , Jian Jie , Huang Jijie , Wang Haiyan
Published: July 2016

Strong exchange bias (EB) in perpendicular direction has been demonstrated in vertically aligned nanocomposite (VAN) (La0.7Sr0.3MnO3)1−x : (LaFeO3)x (LSMO:LFO, x = 0.33, 0.5, 0.67) thin films deposited by pulsed laser deposition. Under a moderate magnetic field cooling, an EB field as high as ∼800 Oe is achieved in the VAN film with x = 0.33, suggesting a great potential for its applications in high density memory devices. Such enhanced EB effects in perpendicular direction can be attributed to the high quality epitaxial co-growth of vertically aligned ferromagnetic LSMO and antiferromagnetic LFO phases, and the vertical interface coupling associated with a disordered spin-glass state. The VAN design paves a powerful way for integrating perpendicular EB effect within thin films and provides a new dimension for advanced spintronic devices.
Communication: Vibrational sum-frequency spectrum of the air-water interface, revisited
Authors: Ni Yicun , Skinner J. L.
Published: July 2016

Before 2015, heterodyne-detected sum-frequency-generation experiments on the air-water interface showed the presence of a positive feature at low frequency in the imaginary part of the susceptibility. However, three very recent experiments indicate that this positive feature is in fact absent. Armed with a better understanding, developed by others, of how to calculate sum-frequency spectra, we recalculate the spectrum and find good agreement with these new experiments. In addition, we provide a revised interpretation of the spectrum.
Controlled Synthesis of PCL/PVP Copolymer by RAFT Method and Its Hydrophilic Block-Dependent Micellar Behaviors
Authors: Li Rui , Pang Wen-min , Zhu Qing-ren , Nie Kang-ming
Published: July 2016

A range of poly(ε-caprolactone)/poly(N-vinyl-2-pyrrolidone) amphiphilic block copolymers with well-defined hydrophilic chain length were synthesized by the living/controlled reversible addition fragmentation chain transfer polymerization method. The composition and structure of the targeted resultants were characterized with 1H NMR, 13C NMR, FT-IR spectroscopy and gel permeation chromatography. The various block copolymers were successfully employed to fabricate the spherical micelle with core-shell morphological structure. The poly(N-vinyl-2-pyrrolidone) block-dependent characteristics of the copolymeric micelles were investigated by fluorescence spectroscopy dynamic light scattering, and transmission electron microscopy. The solubilization of the hydrophobic ibuprofen as a model drug in the micelle solution was also explored. It was found that the drug loading contents are related to the micellar morphology structure determined by hydrophilic chain length in the copolymer.
Investigation of Ultrafast Electronic Transfer Process on Organic/Inorganic Heterojunction by Femtosecond Transient Absorption
Authors: Li Xue-cong , Sui Ning , Liu Qing-hui , Yuan Qi-lin , Wang Ying-hui
Published: July 2016

We detect a relaxation process of excited SQ02 dye in the chlorobenzene solution and anchor SQ02 on Al2O3 and TiO2 film, so as to investigate the photophysical properties of pristine SQ02 in the monodisperse system, aggregation state, and the corresponding interfacial electron transfer process. The experimental data show that the lifetime of SQ02 in the monondisperse system is ∼2.0 ns, but that of SQ02 anchored on the Al2O3 film could obviously decrease to ∼21 ps. The time of electron transfer from excited SQ02 to TiO2 film is estimated to be ∼2.6 ps and the yield of electron injection is estimated to be ∼89.1%, which matches the incident photon to current efficiency of dye-sensitized solar cell based on SQ02. In addition, some dyes are found to pack on the other dyes anchored on the nanocrystal film, and their relaxation time could reach ∼60 ps. They couldn't participate in the interfacial electron transfer, since they are far away from the TiO2 interface.
Morphology and Growth Process of Bat-like ZnO Crystals by Thermal Evaporation
Authors: Gao Pin , Wang Kai , Huang Chao , Meng Lu , Xu Fa-qiang
Published: July 2016

A novel bat-like ZnO nanostructure was synthesized on the silicon substrate by simple thermal evaporation of zinc powders without any catalyst. Each bat-like nanorod (“nanobat”) is composed of a hexagonal head, a continuous neck and a thin handle. High-resolution transmission electron microscopy and selected area electron diffraction results reveal the single-crystalline feature and the growing direction along [0001] of the nanobat. The vapor-solid mechanism was found suitable to explain the growth process of the nanobat and a schematic model was proposed in detail based on the experimental results.
Chapter 7. When L1 suffers
Authors: Christoffels Ingrid , Ganushchak Lesya , La Heij Wido
Published: July 2016

Bilingual language selection and control is often studied in the language switching paradigm, where participants switch between producing words in one or the other language. Although naming in L1 is usually fastest, in language switching studies L1 naming is sometimes found to be slower than L2 naming (e.g., Christoffels, Firk, & Schiller, 2007; Costa & Santesteban, 2004; Gollan & Ferreira, 2009). This “reversed language effect” may be explained by sustained and global inhibition of the L1 in a mixed language context. We studied the scope and duration of this effect by addressing the consequences of mixed language use on later L1 production. Unbalanced bilinguals named the same pictures in Dutch (L1) and English (L2) before and after a central language switching task. In Experiment 1, after an extensive switching task, a reversed language effect was obtained: L1 naming became slower than L2 naming. In Experiment 2 we replicated this reversed language effect and showed that L1 slowing (a) is not limited to the set of words used in the central switching task and (b) is still present after a 10-minutes break. This global and sustained effect on L1 is a clear signature of language control that may be taken as support for sustained L1 inhibition.
Chapter 8. Effects of cognitive control, lexical robustness, and frequency of codeswitching on language switching
Authors: Schwieter John W. , Ferreira Aline
Published: July 2016

This study explores the effects of individual differences on the production of words when switching between a strong and significantly weaker language. Variables of interest included non-linguistic cognitive control, lexical robustness (i.e., the size and strength of the lexicon), and frequency of codeswitching in daily life. Seventy university students who were English (L1) speakers learning Spanish (L2) and French (L3) completed a language questionnaire and participated in: a Simon task; lexical robustness measures in all three languages; and a picture-naming task involving cued language switching between the L1 and L2. The results suggested that cognitive control and L2 lexical robustness had modulating effects on language switching, but only in limited cases. L3 lexical robustness did not affect L1-L2 language switching, however, both L1 and L2 lexical robustness had differential influences, with smaller differences between L1 and L2 switch costs being related to higher levels of L2. Counterintuitively, participants who reported more frequently codeswitching in daily life showed larger switch costs in both L1 and L2. We discuss the implications for these findings and emphasize the importance of examining a more comprehensive spectrum of variables that explain how multilingual experiences shape the networks that support cognition and language regulatory processes.
Chapter 12. The bilingual advantage in the auditory domain
Authors: Ouzia Julia , Filippi Roberto
Published: July 2016

Research on bilingualism has often produced evidence for a bilingual advantage in interference control using visual paradigms such as the Simon Task (e.g., Bialystok, Craik, Klein, & Viswanathan, 2004) or the Attention Network Test (ANT; Costa, Hernández, & Sebastián-Gallés, 2008). Surprisingly, given that bilingual speakers must disentangle auditory messages, there is a dearth of work examining a bilingual advantage in the auditory modality. The aim of this chapter is to evaluate the most relevant literature in this field and to address future directions for this line of enquiry within developmental psychology, educational psychology, and cognitive neuroscience.
Chapter 16. Time course differences between bilinguals and monolinguals in the Simon task*
Authors: Narra Manjunath , Heathcote Andrew , Finkbeiner Matthew
Published: July 2016

In the Simon task, individuals need to indicate the colour of the target stimulus while ignoring its spatial location. The Simon Effect refers to the finding that participants respond more quickly when the target stimulus and response effector are spatially compatible compared to when they are not. Thus, to optimize performance in the Simon task, individuals need to ignore the task-irrelevant (spatial) information and attend to the task-relevant (colour) information. Interestingly, it has been reported that bilinguals are faster than monolinguals in the Simon task and that they exhibit a smaller Simon effect. The present study investigates whether this so-called bilingual advantage is due to bilinguals being better at ignoring task-irrelevant information, or better at activating task-relevant information, or both. In a button-press version of the task, we do not observe a bilingual advantage, but in a reach-to-touch paradigm, we find that bilinguals suppress task-irrelevant information for longer and activate task-relevant information sooner.
EFFE-Escreves como falas – falas como escreves?
Authors: Lourenço Gomes Maria do Carmo , Rodrigues Celeste , Alves Isabel
Published: July 2016

This paper introduces the project EFFE that applies and develops a methodology for data collection primarily intended for the study of the correlation between oral and written production in European Portuguese, and that also aims to serve a broad range of studies in different areas. It comprehends (i) a brief review of two scientific contexts occupied with learning to read and write, which are at the basis of the methodological planning of future corpora; (ii) the methodology adopted for the collection of speech and writing material of 48 children of a private school in Lisbon, and a summary of the quantitative data already observed; (iii) some considerations on unconventional forms (UF) observed in written production that reflect the speech of those children.
Regulatory effects of the L-lysine metabolites, L-2-aminoadipic acid and L-pipecolic acid, on protein turnover in C2C12 myotubes
Authors: Sato Tomonori , Ito Yoshiaki , Nagasawa Takashi
Published: July 2016

We previously showed that L-lysine (Lys) and a metabolite of Lys, L-saccharopine, suppressed autophagic proteolysis in C2C12 myotubes. However, the effects of other metabolites of Lys on protein turnover were unknown. We here investigated the effect of the Lys metabolites, L-2-aminoadipic acid (2-AA) and L-pipecolic acid (Pip), on protein turnover in C2C12 myotubes. 2-AA suppressed myofibrillar protein degradation evaluated by the 3-methylhistidine and autophagy activity evaluated by light chain 3-II at lower concentration (100 μM) than did Lys. On the other hand, Pip stimulated the mammalian target of rapamycin signaling activity. Additionally, 100 μM Pip significantly increased the rates of protein synthesis whereas 100 μM Lys had no effect. These results indicate that in C2C12 myotubes, 2-AA could suppress autophagy and Pip could stimulate the rates of protein synthesis, and these metabolites may contribute to exert effect of Lys on protein turnover.
An investigation of spatial representation of pitch in individuals with congenital amusia
Authors: Lu Xuejing , Sun Yanan , Thompson William Forde
Published: July 2016

Spatial representation of pitch plays a central role in auditory processing. However, it is unknown whether impaired auditory processing is associated with impaired pitch–space mapping. Experiment 1 examined spatial representation of pitch in individuals with congenital amusia using a stimulus–response compatibility (SRC) task. For amusic and non-amusic participants, pitch classification was faster and more accurate when correct responses involved a physical action that was spatially congruent with the pitch height of the stimulus than when it was incongruent. However, this spatial representation of pitch was not as stable in amusic individuals, revealed by slower response times when compared with control individuals. One explanation is that the SRC effect in amusics reflects a linguistic association, requiring additional time to link pitch height and spatial location. To test this possibility, Experiment 2 employed a colour-classification task. Participants judged colour while ignoring a concurrent pitch by pressing one of two response keys positioned vertically to be congruent or incongruent with the pitch. The association between pitch and space was found in both groups, with comparable response times in the two groups, suggesting that amusic individuals are only slower to respond to tasks involving explicit judgments of pitch.
53BP1 and USP28 mediate p53 activation and G1 arrest after centrosome loss or extended mitotic duration
Authors: Meitinger Franz , Anzola John V. , Kaulich Manuel , Richardson Amelia , Stender Joshua D. , Benner Christopher , Glass Christopher K. , Dowdy Steven F. , Desai Arshad , Shiau Andrew K. , Oegema Karen
Published: July 2016

In normal human cells, centrosome loss induced by centrinone—a specific centrosome duplication inhibitor—leads to irreversible, p53-dependent G1 arrest by an unknown mechanism. A genome-wide CRISPR/Cas9 screen for centrinone resistance identified genes encoding the p53-binding protein 53BP1, the deubiquitinase USP28, and the ubiquitin ligase TRIM37. Deletion of TP53BP1, USP28, or TRIM37 prevented p53 elevation in response to centrosome loss but did not affect cytokinesis failure–induced arrest or p53 elevation after doxorubicin-induced DNA damage. Deletion of TP53BP1 and USP28, but not TRIM37, prevented growth arrest in response to prolonged mitotic duration. TRIM37 knockout cells formed ectopic centrosomal-component foci that suppressed mitotic defects associated with centrosome loss. TP53BP1 and USP28 knockouts exhibited compromised proliferation after centrosome removal, suggesting that centrosome-independent proliferation is not conferred solely by the inability to sense centrosome loss. Thus, analysis of centrinone resistance identified a 53BP1-USP28 module as critical for communicating mitotic challenges to the p53 circuit and TRIM37 as an enforcer of the singularity of centrosome assembly.
Mitotic cells get a stress test
Authors: Short Ben
Published: July 2016

Two studies identify a signaling pathway that arrests cells that are having difficulty dividing.
TNF activation of NF-κB is essential for development of single-positive thymocytes
Authors: Webb Louise V. , Ley Steven C. , Seddon Benedict
Published: July 2016

NF-κB activation has been implicated at multiple stages of thymic development of T cells, during which it is thought to mediate developmental signals originating from the T cell receptor (TCR). However, the Card11–Bcl10–Malt1 (CBM) complex that is essential for TCR activation of NF-κB in peripheral T cells is not required for thymocyte development. It has remained unclear whether the TCR activates NF-κB independent of the CBM complex in thymocyte development or whether another NF-κB activating receptor is involved. In the present study, we generated mice in which T cells lacked expression of both catalytic subunits of the inhibitor of κB kinase (IKK) complex, IKK1 and IKK2, to investigate this question. Although early stages of T cell development were unperturbed, maturation of CD4 and CD8 single-positive (SP) thymocytes was blocked in mice lacking IKK1/2 in the T cell lineage. We found that IKK1/2-deficient thymocytes were specifically sensitized to TNF-induced cell death in vitro. Furthermore, the block in thymocyte development in IKK1/2-deficient mice could be rescued by blocking TNF with anti-TNF mAb or by ablation of TNFRI expression. These experiments reveal an essential role for TNF activation of NF-κB to promote the survival and development of single positive T cells in the thymus.
Mutations in STN1 cause Coats plus syndrome and are associated with genomic and telomere defects
Authors: Simon Amos J. , Lev Atar , Zhang Yong , Weiss Batia , Rylova Anna , Eyal Eran , Kol Nitzan , Barel Ortal , Cesarkas Keren , Soudack Michalle , Greenberg-Kushnir Noa , Rhodes Michele , Wiest David L. , Schiby Ginette , Barshack Iris , Katz Shulamit , Pras Elon , Poran Hana , Reznik-Wolf Haike , Ribakovsky Elena , Simon Carlos , Hazou Wadi , Sidi Yechezkel , Lahad Avishay , Katzir Hagar , Sagie Shira , Aqeilan Haifa A. , Glousker Galina , Amariglio Ninette , Tzfati Yehuda , Selig Sara , Rechavi Gideon , Somech Raz
Published: July 2016

The analysis of individuals with telomere defects may shed light on the delicate interplay of factors controlling genome stability, premature aging, and cancer. We herein describe two Coats plus patients with telomere and genomic defects; both harbor distinct, novel mutations in STN1, a member of the human CTC1–STN1–TEN1 (CST) complex, thus linking this gene for the first time to a human telomeropathy. We characterized the patients’ phenotype, recapitulated it in a zebrafish model and rescued cellular and clinical aspects by the ectopic expression of wild-type STN1 or by thalidomide treatment. Interestingly, a significant lengthy control of the gastrointestinal bleeding in one of our patients was achieved by thalidomide treatment, exemplifying a successful bed-to-bench-and-back approach.
Conformational heterogeneity in closed and open states of the KcsA potassium channel in lipid bicelles
Authors: Kim Dorothy M. , Dikiy Igor , Upadhyay Vikrant , Posson David J. , Eliezer David , Nimigean Crina M.
Published: July 2016

The process of ion channel gating—opening and closing—involves local and global structural changes in the channel in response to external stimuli. Conformational changes depend on the energetic landscape that underlies the transition between closed and open states, which plays a key role in ion channel gating. For the prokaryotic, pH-gated potassium channel KcsA, closed and open states have been extensively studied using structural and functional methods, but the dynamics within each of these functional states as well as the transition between them is not as well understood. In this study, we used solution nuclear magnetic resonance (NMR) spectroscopy to investigate the conformational transitions within specific functional states of KcsA. We incorporated KcsA channels into lipid bicelles and stabilized them into a closed state by using either phosphatidylcholine lipids, known to favor the closed channel, or mutations designed to trap the channel shut by disulfide cross-linking. A distinct state, consistent with an open channel, was uncovered by the addition of cardiolipin lipids. Using selective amino acid labeling at locations within the channel that are known to move during gating, we observed at least two different slowly interconverting conformational states for both closed and open channels. The pH dependence of these conformations and the predictable disruptions to this dependence observed in mutant channels with altered pH sensing highlight the importance of conformational heterogeneity for KcsA gating.
H&E-stained Whole Slide Image Deep Learning Predicts SPOP Mutation State in Prostate Cancer
Authors: Schaumberg Andrew J. , Rubin Mark A. , Fuchs Thomas J.
Published: July 2016

A quantitative model to genetically interpret the histology in whole microscopy slide images is desirable to guide downstream immuno-histochemistry, genomics, and precision medicine. We constructed a statistical model that predicts whether or not SPOP is mutated in prostate cancer, given only the digital whole slide after standard hematoxylin and eosin [H&E] staining. Using a TCGA cohort of 177 prostate cancer patients where 20 had mutant SPOP, we trained multiple ensembles of residual networks, accurately distinguishing SPOP mutant from SPOP non-mutant patients (test AUROC=0.74, p=0.0007 Fisher’s Exact Test). We further validated our full metaensemble classifier on an independent test cohort from MSK-IMPACT of 152 patients where 19 had mutant SPOP. Mutants and non-mutants were accurately distinguished despite TCGA slides being frozen sections and MSK-IMPACT slides being formalin-fixed paraffin-embedded sections (AUROC=0.86, p=0.0038). Moreover, we scanned an additional 36 MSK-IMPACT patients having mutant SPOP, trained on this expanded MSK-IMPACT cohort (test AUROC=0.75, p=0.0002), tested on the TCGA cohort (AUROC=0.64, p=0.0306), and again accurately distinguished mutants from non-mutants using the same pipeline. Importantly, our method demonstrates tractable deep learning in this “small data” setting of 20-55 positive examples and quantifies each prediction’s uncertainty with confidence intervals. To our knowledge, this is the first statistical model to predict a genetic mutation in cancer directly from the patient’s digitized H&E-stained whole microscopy slide. Moreover, this is the first time quantitative features learned from patient genetics and histology have been used for content-based image retrieval, finding similar patients for a given patient where the histology appears to share the same genetic driver of disease i.e. SPOP mutation (p=0.0241 Kost’s Method), and finding similar patients for a given patient that does not have have that driver mutation (p=0.0170 Kost’s Method).

Significance Statement

This is the first pipeline predicting gene mutation probability in cancer from digitized H&E-stained microscopy slides. To predict whether or not the speckle-type POZ protein [SPOP] gene is mutated in prostate cancer, the pipeline (i) identifies diagnostically salient slide regions, (ii) identifies the salient region having the dominant tumor, and (iii) trains ensembles of binary classifiers that together predict a confidence interval of mutation probability. Through deep learning on small datasets, this enables automated histologic diagnoses based on probabilities of underlying molecular aberrations and finds histologically similar patients by learned genetic-histologic relationships.

Conception, Writing: AJS, TJF. Algorithms, Learning, CBIR: AJS. Analysis: AJS, MAR, TJF. Supervision: MAR, TJF.
Bayesian model reveals latent atrophy factors with dissociable cognitive trajectories in Alzheimer’s disease
Authors: Zhang Xiuming , Mormino Elizabeth C. , Sun Nanbo , Sperling Reisa A. , Sabuncu Mert R. , Yeo B.T. Thomas ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: July 2016

We employed a data-driven Bayesian model to automatically identify distinct latent factors of overlapping atrophy patterns from voxelwise structural magnetic resonance imaging (MRI) of late-onset Alzheimer’s disease (AD) dementia patients. Our approach estimated the extent to which multiple distinct atrophy patterns were expressed within each participant rather than assuming that each participant expressed a single atrophy factor. The model revealed a temporal atrophy factor (medial temporal cortex, hippocampus and amygdala), a subcortical atrophy factor (striatum, thalamus and cerebellum), and a cortical atrophy factor (frontal, parietal, lateral temporal and lateral occipital cortices). To explore the influence of each factor in early AD, atrophy factor compositions were inferred in beta-amyloid-positive (Aβ+) mild cognitively impaired (MCI) and cognitively normal (CN) participants. All three factors were associated with memory decline across the entire clinical spectrum, whereas the cortical factor was associated with executive function decline in Aβ+ MCI participants and AD dementia patients. Direct comparison between factors revealed that the temporal factor showed the strongest association with memory, while the cortical factor showed the strongest association with executive function. The subcortical factor was associated with the slowest decline for both memory and executive function compared to temporal and cortical factors. These results suggest that distinct patterns of atrophy influence decline across different cognitive domains. Quantification of this heterogeneity may enable the computation of individual-level predictions relevant for disease monitoring and customized therapies. Code from this manuscript is publicly available at link_to_be_added.
Multidrug-resistant pathogens isolated from ready-to-eat salads available at a local market in Pakistan
Authors: Ilyas Sana , Qamar Muhammad  Usman , Rasool Muhammad Hidayat , Abdulhaq Nazia , Nawaz Zeeshan
Published: July 2016

Purpose

– The purpose of this paper is to evaluate the frequency and antimicrobial susceptibility pattern of pathogens present in ready-to-eat salads available at a local market.

Design/methodology/approach

– A 100 salad samples were collected aseptically. Each sample (25 g) was homogenized in 225 ml of sterile peptone water and was serially diluted up to 1×106. Dilutions were inoculated on nutrient agar by surface spread plate technique. Aerobic colony count (ACC) was estimated by counting the colonies. Bacterial isolates were cultured on blood and MacConkey agar and identified on the basis of their morphology, culture characteristics and confirmed by API 20E and 20NE. Antimicrobial susceptibility was determined as per CLSI 2014.

Findings

– ACC range was 1.1×103 cfu/g to 5.8×109 cfu/g. Among these the highest ACC was found in channa chat (4.9×104 to 5.8×109 cfu/g). A total of 127 microorganisms were identified; 73 were gram negative rods (GNRs) and 24 were gram positive cocci (GPC). Among GNRs; Klebsiella spp. (n=18) was the predominant whereas among GPC, Staphylococcus aureus (n=6) were the chief pathogen. Klebsiella spp. showed 100 percent resistance to ampicillin, 89-78 percent to amoxicillin/clavulanic acid and 33 percent to imipenem, however, Enterobacter spp. were resistant to ampicillin (100 percent) amoxicillin/clavulanic acid (77 percent) and imipenem (23 percent). Staphylococcus aureus showed resistance to co-amoxiclav (83 percent) and penicillin (75 percent).

Practical implications

– This study revealed that effective control measures must been implemented and respected by throughout the entire food chain and better surveillance studies should be performed at national level to reduce the spread of bacteria by fresh salads.

Originality/value

– This paper explore the high prevalence of multidrug-resistant pathogens in different salads and most of the salads were found to be unhygienic for consumption.
Consumer perceptions of free-range laying hen welfare
Authors: Pettersson Isabelle Claire , Weeks Claire Alexandra , Wilson Lorna Rachel Maven , Nicol Christine Janet
Published: July 2016

Purpose

– The purpose of this paper is to understand which factors and resources free-range egg consumers believe are important for hen welfare.

Design/methodology/approach

– An online survey was distributed via the mailing list of a UK free-range egg brand receiving 6,378 responses. The survey was mostly five-point Likert-scale based. The same survey was also distributed to a group of animal welfare specialists receiving 34 responses.

Findings

– Respondents bought free-range eggs because hens are “happier” (74.2 per cent) and “healthier” (69.0 per cent) and because they believed such eggs to taste better (57.9 per cent). They rated all the suggested factors that might contribute to hen welfare as “important” or “very important” (on average) but believed outside access and fresh air to be most important. Respondents rated the suitability of resources relating to behavioural needs high (“suitable” or “very suitable”) indoors and shelter as the most suitable outdoors. Consumers differed from welfare specialists in their views on factors contributing to hen welfare, but their views on resource suitability were similar.

Research limitations/implications

– The sample was biased towards free-range egg consumers who had expressed an interest in a brand marketed as high welfare.

Originality/value

– This is the first study to ask consumers what they consider to be important for hen welfare and how they think hen welfare can be improved. Because consumers can affect on-farm welfare through their purchasing habits assessing the degree of agreement between consumers and animal welfare specialists is important.
Food fraud and consumers’ choices in the wake of the horsemeat scandal
Authors: Agnoli Lara , Capitello Roberta , De Salvo Maria , Longo Alberto , Boeri Marco
Published: July 2016

Purpose

– In 2012, the European food industry was hit by a food fraud: horsemeat was found in pre-prepared foods, without any declaration on the package. This is commonly referred to as the “horsemeat scandal”. The purpose of this paper is to investigate consumers’ preferences across Europe for a selected ready meal, ready to heat (RTH) fresh lasagne, to consider whether the effects of potential food frauds on consumers’ choices can be mitigated by introducing enhanced standards of RTH products.

Design/methodology/approach

– An online survey was administered to 4,598 consumers of RTH lasagne in six European countries (Republic of Ireland, France, Italy, Spain, Germany and Norway), applying discrete choice experiments to estimate consumers’ willingness to pay for enhanced food safety standards and highlight differences between countries.

Findings

– Many similarities across countries emerged, as well as some differences. Consumers in Europe are highly concerned with the authenticity of the meat in ready meals and strongly prefer to know that ingredients are nationally sourced. Strong regional differences in price premiums exist for enhanced food safety standards.

Originality/value

– This research adds relevant insights in the analysis of consumers’ reaction to food fraud, providing practical guidelines on the most appropriate practices that producers should adopt and on the information to reduce food risk perception among consumers. This would prove beneficial for the food processing industry and the European Union. The survey is based on a representative sample of European consumers making this the largest cross-country study of this kind.
Origin based agro-food products: how to communicate their experiential value online?
Authors: Iaia Lea , Maizza Amedeo , Fait Monica , Scorrano Paola
Published: July 2016

Purpose

– The purpose of this paper is to investigate the experiential dimension of certain Italian agrofood products’ websites, which are seen as exemplifying best practices in the terms of the representation of the brand-land relationship, including their link with the territory of origin in the sense of terroir.

Design/methodology/approach

– The study was conducted after the conception and experimentation of a model (called SObER), the fruit of detailed studies of experiential marketing (Schmitt, 1999a, b). The model was tested using the user-based focus group technique (Mich, 2007) and verified with reference to certain consortia brands considered to reflect best practices in communication of the brand-land connection.

Findings

– The analysis made it possible to identify the key elements for expressing both the experiential dimension and the brand-land relationship of traditional agrofood products, ensuring their effective online communication.

Research limitations/implications

– Although the research uses a benchmarking technique, it focuses on specific case studies; thus, the outcomes can be generalised by means of an extension of the analysis.

Originality/value

– The value of the analysis carried out lies in the creation of a model aimed at the assessment of agrofood products and, more generally, their link with the territory of origin in the online context. In addition, the marketing literature on the experiential dimension applied to website tools is still limited. For this reason, this work may stimulate future in-depth analysis with reference to the proposed model.
Citizens’ perception of modern pig production in Germany: a mixed-method research approach
Authors: Weible Daniela , Christoph-Schulz Inken , Salamon Petra , Zander Katrin
Published: July 2016

Purpose

– The wide divergence of the people’s expectations and agricultural reality results in conflicts between the agricultural sector and the general public. Contemporary animal husbandry systems are being increasingly critically addressed by media; however, there is no information about peoples’ perceptions and attitudes concentrating precisely on specific animal husbandry systems. The purpose of this paper is to explore citizens’ perceptions, expectations and main points of criticism in regard to intensive pig production in Germany, and to identify and describe distinct population groups reflecting different attitudes.

Design/methodology/approach

– A mixed method approach combining qualitative focus groups with a quantitative online survey has been employed. Focus groups capture a wide variety of opinions and concerns in an exploratory manner. Based on these findings, the quantitative survey (n=1,500 citizens) allowed the identification and characterisation of population groups with identical attitudes regarding pig husbandry.

Findings

– Qualitative research uncovered a huge range of criticism on pig husbandry, e.g. lack of space, frequency and prophylactic use of medications as well as a lack of care. A relationship was seen between the lack of space, widespread use of medications and behavioural disorders. Consumer preferences for buying cheap meat were believed to be part of the problem since this behaviour fosters the development of larger farms. Quantitative research confirmed the generally critical perception and identified three population groups. Only one third of the population was really concerned about animal husbandry. Younger people and people with better knowledge of agriculture were stronger opponents of intensive pig husbandry.

Practical implications

– Results indicate that increasing people’s knowledge may have an adverse effect on their acceptance of modern farming systems. More communication and better information strategies will probably not improve societal acceptance by itself. Instead, agricultural production systems need to be improved to meet better consumers’ expectations whereas communicating these improvements to consumers and the general public in a well-targeted manner will be required as well.

Originality/value

– When considering options for enhancing public acceptance of modern animal husbandry, a combination of different strategies by different stakeholders is needed. The agricultural sector should improve its communication with the general public and rethink its production practices against the background of public expectations. The government and its agencies urgently need to improve monitoring of the compliance of actual production practices with existing laws and to enforce them. Additionally, adjustments of current regulations of animal husbandry in light of public expectations should be considered.