bluuebunny/crossref_metadata_2025 huggingface dataset:
The ab-initio density matrix renormalization group in practice
Authors: Olivares-Amaya Roberto , Hu Weifeng , Nakatani Naoki , Sharma Sandeep , Yang Jun , Chan Garnet Kin-Lic
Published: January 2015

The ab-initio density matrix renormalization group (DMRG) is a tool that can be applied to a wide variety of interesting problems in quantum chemistry. Here, we examine the density matrix renormalization group from the vantage point of the quantum chemistry user. What kinds of problems is the DMRG well-suited to? What are the largest systems that can be treated at practical cost? What sort of accuracies can be obtained, and how do we reason about the computational difficulty in different molecules? By examining a diverse benchmark set of molecules: π-electron systems, benchmark main-group and transition metal dimers, and the Mn-oxo-salen and Fe-porphine organometallic compounds, we provide some answers to these questions, and show how the density matrix renormalization group is used in practice.
A large-dynamic-range current probe for microsecond pulsed vacuum breakdown research
Authors: Zhao Liang , Su Jian-cang , Zhang Xi-bo , Li Rui , Zheng Lei , Zeng Bo , Cheng Jie , She Xi-yuan , Wu Xiao-long
Published: January 2015

A large-dynamic-range current probe for microsecond pulsed vacuum breakdown research is fabricated. The basic principle of this probe is to turn the current signal to a voltage one via a load of fixed impedance and to test the voltage signal via a voltage divider of adjustable voltage ratio. With a segment of 40-Ω coaxial line, which is connected to the experimental chamber, and a self-fabricated two-stage resistor-capacitor voltage divider, the current probe is realized and is applied to test the vacuum breakdown current for 3-cm parallel-plate electrodes under microsecond pulses. The results show that the current probe is capable of responding to current signals with an amplitude of 10−2-103 A and a duration of 10−2-101 μs. Based on the current probe, the characteristics of the vacuum breakdown current under 30-μs quasi-sinusoidal pulses are summarized. The potential mechanisms for each type of current are also discussed in this paper.
Solutions and reductions for radiative energy transport in laser-heated plasma
Authors: Broadbridge P. , Ivanova N. M.
Published: January 2015

A full symmetry classification is given for models of energy transport in radiant plasma when the mass density is spatially variable and the diffusivity is nonlinear. A systematic search for conservation laws also leads to some potential symmetries and to an integrable nonlinear model. Classical point symmetries, potential symmetries, and nonclassical symmetries are used to effect variable reductions and exact solutions. The simplest time-dependent solution is shown to be stable and relevant to a closed system.
Stabilized quasi-Newton optimization of noisy potential energy surfaces
Authors: Schaefer Bastian , Alireza Ghasemi S. , Roy Shantanu , Goedecker Stefan
Published: January 2015

Optimizations of atomic positions belong to the most commonly performed tasks in electronic structure calculations. Many simulations like global minimum searches or characterizations of chemical reactions require performing hundreds or thousands of minimizations or saddle computations. To automatize these tasks, optimization algorithms must not only be efficient but also very reliable. Unfortunately, computational noise in forces and energies is inherent to electronic structure codes. This computational noise poses a severe problem to the stability of efficient optimization methods like the limited-memory Broyden–Fletcher–Goldfarb–Shanno algorithm. We here present a technique that allows obtaining significant curvature information of noisy potential energy surfaces. We use this technique to construct both, a stabilized quasi-Newton minimization method and a stabilized quasi-Newton saddle finding approach. We demonstrate with the help of benchmarks that both the minimizer and the saddle finding approach are superior to comparable existing methods.
Optical microscope and tapered fiber coupling apparatus for a dilution refrigerator
Authors: MacDonald A. J. R. , Popowich G. G. , Hauer B. D. , Kim P. H. , Fredrick A. , Rojas X. , Doolin P. , Davis J. P.
Published: January 2015

We have developed a system for tapered fiber measurements of optomechanical resonators inside a dilution refrigerator, which is compatible with both on- and off-chip devices. Our apparatus features full three-dimensional control of the taper-resonator coupling conditions enabling critical coupling, with an overall fiber transmission efficiency of up to 70%. Notably, our design incorporates an optical microscope system consisting of a coherent bundle of 37 000 optical fibers for real-time imaging of the experiment at a resolution of ∼1 μm. We present cryogenic optical and optomechanical measurements of resonators coupled to tapered fibers at temperatures as low as 9 mK.
Temperature cross-sensitivity characteristics of singlemode–multimode–singlemode fiber structure
Authors: Zhang Rongxiang , Liu Tiegen , Han Qun , Chen Yaofei , Li Lin , Yao X. Steve
Published: January 2015

The temperature cross-sensitivity characteristics of a singlemode–multimode–singlemode (SMS) fiber structure packaged by a shell are studied both theoretically and experimentally. By theoretical investigation, we found that the temperature sensitivity of a SMS structure is mainly determined by the thermo-optic effect (TOE) of the cladding of the multimode fiber (MMF). Meanwhile, the TOE of the MMF core, thermal expansion effects (TEEs) of the MMF core, and the packaging material also influence the ultimate sensitivity, and the magnitude of their effects depends on the refractive index of the MMF cladding. Among them, the TEE of the packaging material, inducing an axial strain, is considered to be the second main factor. A temperature sensor based on a packaged SMS structure is designed and investigated to experimentally verify the theoretical findings. The experimentally measured temperature sensitivity of the sensor is −453.4 pm/°C, which agrees well with the theoretical prediction.
Optical properties of transition metal oxide quantum wells
Authors: Lin Chungwei , Posadas Agham , Choi Miri , Demkov Alexander A.
Published: January 2015

Fabrication of a quantum well, a structure that confines the electron motion along one or more spatial directions, is a powerful method of controlling the electronic structure and corresponding optical response of a material. For example, semiconductor quantum wells are used to enhance optical properties of laser diodes. The ability to control the growth of transition metal oxide films to atomic precision opens an exciting opportunity of engineering quantum wells in these materials. The wide range of transition metal oxide band gaps offers unprecedented control of confinement while the strong correlation of d-electrons allows for various cooperative phenomena to come into play. Here, we combine density functional theory and tight-binding model Hamiltonian analysis to provide a simple physical picture of transition metal oxide quantum well states using a SrO/SrTiO3/SrO heterostructure as an example. The optical properties of the well are investigated by computing the frequency-dependent dielectric functions. The effect of an external electric field, which is essential for electro-optical devices, is also considered.
Some remarks on representations of Yang-Mills algebras
Authors: Herscovich Estanislao
Published: January 2015

In this article, we present some new properties of representations of Yang-Mills algebras. We first show that any free Lie algebra with m generators is a quotient of the Yang-Mills algebra 𝔶𝔪(n) on n generators, for n ≥ 2m. We derive from this that any semisimple Lie algebra and even any affine Kac-Moody algebra is a quotient of 𝔶𝔪(n) for n ≥ 4. Combining this with previous results on representations of Yang-Mills algebras given in [Herscovich and Solotar, Ann. Math. 173(2), 1043–1080 (2011)], one may obtain solutions to the Yang-Mills equations by differential operators acting on sections of twisted vector bundles on the affine space of dimension n ≥ 4 associated to representations of any semisimple Lie algebra. We also show that this quotient property does not hold for n = 3, since any morphism of Lie algebras from 𝔶𝔪(3) to 𝔰𝔩(2, k) has in fact solvable image.
Ion beam requirements for fast ignition of inertial fusion targets
Authors: Honrubia J. J. , Murakami M.
Published: January 2015

Ion beam requirements for fast ignition are investigated by numerical simulation taking into account new effects, such as ion beam divergence, not included before. We assume that ions are generated by the TNSA scheme in a curved foil placed inside a re-entrant cone and focused on the cone apex or beyond. From the focusing point to the compressed core, ions propagate with a given divergence angle. Ignition energies are obtained for two compressed fuel configurations heated by proton and carbon ion beams. The dependence of the ignition energies on the beam divergence angle and on the position of the ion beam focusing point has been analyzed. Comparison between TNSA and quasi-monoenergetic ions is also shown.
p-type microcrystalline silicon oxide emitter for silicon heterojunction solar cells allowing current densities above 40 mA/cm2
Authors: Mazzarella L. , Kirner S. , Stannowski B. , Korte L. , Rech B. , Schlatmann R.
Published: January 2015

We have developed a microcrystalline silicon oxide (μc-SiOx:H) p-type emitter layer that significantly improves the light incoupling at the front side of silicon heterojunction solar cells by minimizing reflection losses. The μc-SiOx:H p-layer with a refractive index of 2.87 at 632 nm wavelength and the transparent conducting oxide form a stack with refractive indexes which consecutively decrease from silicon to the ambient air and thus significantly reduce the reflection. Optical simulations performed for flat wafers reveal that the antireflective effect of the emitter overcompensates the parasitic absorption and suggest an ideal thickness of about 40 nm. On textured wafers, the increase in current density is still more than 1 mA/cm2 for a typical emitter thickness of 10 nm. Thus, we are able to fabricate heterojunction solar cells with current densities significantly over 40 mA/cm2 and power conversion efficiency above 20%, which is yet mainly limited by the cell's fill factor.
Circular polarization switching and bistability in an optically injected 1300 nm spin-vertical cavity surface emitting laser
Authors: Alharthi S. S. , Hurtado A. , Korpijarvi V.-M. , Guina M. , Henning I. D. , Adams M. J.
Published: January 2015

We report the experimental observation of circular polarization switching (PS) and polarization bistability (PB) in a 1300 nm dilute nitride spin-vertical cavity surface emitting laser (VCSEL). We demonstrate that the circularly polarized optical signal at 1300 nm can gradually or abruptly switch the polarization ellipticity of the spin-VCSEL from right-to-left circular polarization and vice versa. Moreover, different forms of PS and PB between right- and left-circular polarizations are observed by controlling the injection strength and the initial wavelength detuning. These results obtained at the telecom wavelength of 1300 nm open the door for novel uses of spin-VCSELs in polarization sensitive applications in future optical systems.
Energy in density gradient
Authors: Vranjes J. , Kono M.
Published: January 2015

Inhomogeneous plasmas and fluids contain energy stored in inhomogeneity and they naturally tend to relax into lower energy states by developing instabilities or by diffusion. But the actual amount of energy in such inhomogeneities has remained unknown. In the present work, the amount of energy stored in a density gradient is calculated for several specific density profiles in a cylindrical configuration. This is of practical importance for drift wave instability in various plasmas, and, in particular, in its application in models dealing with the heating of solar corona because the instability is accompanied with stochastic heating, so the energy contained in inhomogeneity is effectively transformed into heat. It is shown that even for a rather moderate increase of the density at the axis in magnetic structures in the corona by a factor 1.5 or 3, the amount of excess energy per unit volume stored in such a density gradient becomes several orders of magnitude greater than the amount of total energy losses per unit volume (per second) in quiet regions in the corona. Consequently, within the life-time of a magnetic structure such energy losses can easily be compensated by the stochastic drift wave heating.
Electrical performance of phase change memory cells with Ge3Sb2Te6 deposited by molecular beam epitaxy
Authors: Boschker Jos E. , Boniardi Mattia , Redaelli Andrea , Riechert Henning , Calarco Raffaella
Published: January 2015

Here, we report on the electrical characterization of phase change memory cells containing a Ge3Sb2Te6 (GST) alloy grown in its crystalline form by Molecular Beam Epitaxy (MBE). It is found that the high temperature growth on the amorphous substrate results in a polycrystalline film exhibiting a rough surface with a grain size of approximately 80–150 nm. A detailed electrical characterization has been performed, including I-V characteristic curves, programming curves, set operation performance, crystallization activation at low temperature, and resistance drift, in order to determine the material related parameters. The results indicate very good alignment of the electrical parameters with the current state-of-the-art GST, deposited by physical vapor deposition. Such alignment enables a possible employment of the MBE deposition technique for chalcogenide materials in the phase change memory technology, thus leading to future studies of as-deposited crystalline chalcogenides as integrated in electrical vehicles.
Synthesized multiwall MoS2 nanotube and nanoribbon field-effect transistors
Authors: Fathipour S. , Remskar M. , Varlec A. , Ajoy A. , Yan R. , Vishwanath S. , Rouvimov S. , Hwang W. S. , Xing H. G. , Jena D. , Seabaugh A.
Published: January 2015

We report on the fabrication and characterization of synthesized multiwall MoS2 nanotube (NT) and nanoribbon (NR) field-effect transistors (FETs). The MoS2 NTs and NRs were grown by chemical transport, using iodine as a transport agent. Raman spectroscopy confirms the material as unambiguously MoS2 in NT, NR, and flake forms. Transmission electron microscopy was used to observe cross sections of the devices after electrical measurements and these were used in the interpretation of the electrical measurements, allowing the estimation of the current density. The NT and NR FETs demonstrate n-type behavior, with ON/OFF current ratios exceeding 103, and with current densities of 1.02 μA/μm and 0.79 μA/μm at VDS = 0.3 V and VBG = 1 V, respectively. Photocurrent measurements conducted on a MoS2 NT FET revealed short-circuit photocurrent of tens of nanoamps under an excitation optical power of 78 μW and 488 nm wavelength, which corresponds to a responsivity of 460 μA/W. A long channel transistor model was used to model the common-source characteristics of MoS2 NT and NR FETs and was shown to be consistent with the measured data.
Cross-type optical separation of elastic oblate capsules in a uniform flow
Authors: Chang Cheong Bong , Huang Wei-Xi , Sung Hyung Jin
Published: January 2015

The dynamic behavior of an elastic capsule with an initially oblate spheroidal shape during cross-type optical separation was numerically investigated. The penalty immersed boundary method was adopted for the fluid-membrane interaction, and the optical force calculation was conducted by using the ray optics method including the ray-surface intersection algorithm. The oblate elastic capsule of b/a = 0.5 with different surface Young's moduli and different initial inclination angles was considered. The oblate capsule with higher surface Young's moduli was less deformed, and was more migrated for each initial inclination angle. Unlike the oblate rigid particle, the initially inclined capsules with moderate inclination angles were similarly migrated since the oblate elastic capsule was deformed during rotation near the laser beam axis. The oblate capsules can be separated according to the surface Young's modulus, except for nearly non-inclined capsules. As the fluid velocity decreased, the migration distance increased. The maximum deformation parameter was insensitive to the fluid velocity. Furthermore, a new dimensionless number (Sec) was introduced to predict the migration distance of the oblate elastic capsule.
Role of elastic deformation in determining the mixed alkaline earth effect of hardness in silicate glasses
Authors: Kjeldsen Jonas , Smedskjaer Morten M. , Potuzak Marcel , Yue Yuanzheng
Published: January 2015

Glasses deform permanently as a result of indentation and the total resistance to deformation consists of three individual resistances, i.e., those to elastic deformation, densification, and plastic flow. The link between Vickers hardness and the resistances to densification and plastic flow has been investigated previously, but the link between the resistance to elastic deformation and hardness has not yet been studied. In this work, we investigate the link between elastic deformation during indentation and Vickers hardness in a series of mixed magnesium-barium boroaluminosilicate glasses. We show that the mixed alkaline earth effect manifests itself as deviations from linearity in shear modulus, Poisson's ratio, glass transition temperature, liquid fragility index, hardness, volume of densification, and volume of plastic flow. We find no correlation between the elastic part of the indentation and hardness, and we thus infer that elastic deformation does not play a dominant role in determining the mixed alkaline earth effect of hardness. However, interestingly, we find a strong correlation between Poisson's ratio, volume of plastic flow, and hardness, by which the minimum in hardness could be explained in terms of a minimum in shear viscosity.
Wave-mixing with high-order harmonics in extreme ultraviolet region
Authors: Dao Lap Van , Dinh Khuong Ba , Le Hoang Vu , Gaffney Naylyn , Hannaford Peter
Published: January 2015

We report studies of the wave-mixing process in the extreme ultraviolet region with two near-infrared driving and controlling pulses with incommensurate frequencies (at 1400 nm and 800 nm). A non-collinear scheme for the two beams is used in order to spatially separate and to characterise the properties of the high-order wave-mixing field. We show that the extreme ultraviolet frequency mixing can be treated by perturbative, very high-order nonlinear optics; the modification of the wave-packet of the free electron needs to be considered in this process.
On the diameter dependence of metal-nanowire Schottky barrier height
Authors: Calahorra Yonatan , Yalon Eilam , Ritter Dan
Published: January 2015

Bardeen's model for the non-ideal metal-semiconductor interface was applied to metal-wrapped cylindrical nanowire systems of 30–400 nm in diameter; a significant effect of the nanowire diameter on the non-ideal Schottky barrier height was found. The calculations were performed by solving Poisson's equation in the nanowire, self-consistently with the constraints set by the non-ideal interface conditions; in these calculations, the barrier height is obtained from the solution, and it is not a boundary condition for Poisson's equation. The main finding is that thin nanowires are expected to have O(10−100) meV higher Schottky barriers compared to their thicker counterparts; an effect 3–4 times stronger than the diameter dependence of image-force barrier lowering in similar systems. What lies behind this effect is the electrostatic properties of metal-wrapped nanowires; in particular, since depletion charge is reduced with nanowire radius, the potential drop on the interfacial layer is reduced—leading to the increase of the barrier height with nanowire radius reduction.
Alternating InGaN barriers with GaN barriers for enhancing optical performance in InGaN light-emitting diodes
Authors: Yang Yujue , Zeng Yiping
Published: January 2015

InGaN-based light-emitting diodes (LEDs) with some specific designs on the quantum barrier layers by alternating InGaN barriers with GaN barriers are proposed and studied numerically. In the proposed structure, simulation results show that the carriers are widely dispersed in the multi-quantum well active region, and the radiative recombination rate is efficiently improved and the electron leakage is suppressed accordingly, due to the appropriate band engineering. The internal quantum efficiency and light-output power are thus markedly enhanced and the efficiency droop is smaller, compared to the original structures with GaN barriers or InGaN barriers. Moreover, the gradually decrease of indium composition in the alternating quantum barriers can further promote the LED performance because of the more uniform carrier distribution, which provides us a simple but highly effective approach for high-performance LED applications.
Strain-induced dimensionality crossover of precursor modulations in Ni2MnGa
Authors: Nie Zhihua , Wang Yandong , Shang Shunli , Zeng Qiaoshi , Ren Yang , Liu Dongmei , Yang Wenge , Wang Yi , Liu Zi-Kui
Published: January 2015

Precursor modulations often occur in functional materials like magnetic shape memory alloys, ferroelectrics, and superconductors. In this letter, we have revealed the underlying mechanism of the precursor modulations in ferromagnetic shape memory alloys Ni2MnGa by combining synchrotron-based x-ray diffraction experiments and first-principles phonon calculations. We discovered the precursor modulations along [011] direction can be eliminated with [001] uniaxial loading, while the precursor modulations or premartensite can be totally suppressed by hydrostatic pressure condition. The TA2 phonon anomaly is sensitive to stress induced lattice strain, and the entire TA2 branch is stabilized along the directions where precursor modulations are eliminated by external stress. Our discovery bridges precursor modulations and phonon anomalies, and sheds light on the microscopic mechanism of the two-step superelasticity in precursor martensite.
Geometric tuning of charge and spin correlations in manganite superlattices
Authors: Rogdakis K. , Viskadourakis Z. , Petrović A. P. , Choi E. , Lee J. , Panagopoulos C.
Published: January 2015

We report a modulation of the in-plane magnetotransport in artificial manganite superlattice [(NdMnO3)n/(SrMnO3)n/(LaMnO3)n]m by varying the layer thickness n while keeping the total thickness of the structure constant. Charge transport in these heterostructures is confined to the interfaces and occurs via variable range hopping. Upon increasing n, the interfacial separation rises, leading to a suppression of the electrostatic screening between carriers of neighboring interfaces and the opening of a Coulomb gap at the Fermi level (EF). The high-field magnetoresistance (MR) is universally negative due to progressive spin alignment. However, at a critical thickness of n = 5 unit cells (u.c.), an exchange field coupling between ferromagnetically ordered interfaces results in positive MR at low magnetic field (H). Our results demonstrate the ability to geometrically tune the electrical transport between regimes dominated by either charge or spin correlations.
Seminal CD38 is a pivotal regulator for fetomaternal tolerance
Authors: Kim Byung-Ju , Choi Yun-Min , Rah So-Young , Park Dae-Ryoung , Park Seon-Ah , Chung Yun-Jo , Park Seung-Moon , Park Jong Kwan , Jang Kyu Yun , Kim Uh-Hyun
Published: January 2015

Significance

In natural matings, semen delivers spermatozoa and immunoregulatory fluids to the female reproductive tract. Here, a soluble form of CD38 (sCD38) is shown to play an important role in facilitating maternal immune tolerance against the fetus by inducing the development of uterine tolerogenic DCs and forkhead box P3+(Foxp3+) regulatory T cells. Deficiency of sCD38 in seminal fluid increased the rates of loss of allogeneic fetuses, and this loss was rescued by a direct injection of recombinant sCD38 into the uterus. Thus, seminal sCD38 acts as a pivotal immune suppressor for establishing maternal immune tolerance against the fetus. sCD38 could potentially be used to prevent failed pregnancies.
Femtosecond filamentation induced fluorescence technique for atmospheric sensing*
Authors: Yuan Shuai , Chin See Leang , Zeng He-Ping
Published: January 2015

Recent progress in filament-induced atmospheric sensing is reviewed. Self-guided propagation of ultrashort laser pulses in air induces laser filamentation. All molecules in the path of a filament can be dissociated into highly excited fragments, resulting in emission of characteristic fluorescence spectra. The fluorescence spectra provide information about the various molecules in the filaments. By using a filament-induced “fingerprinting” fluorescence technique, molecules in the atmosphere can be identified.
A note on condensations of function spaces onto 𝜎-compact and analytic spaces
Authors: Krupski Mikołaj
Published: January 2015

Modifying a construction of W. Marciszewski we prove (in ZFC) that there exists a subspace

X
X

of the real line

R

\mathbb {R}

, such that the realcompact space

C
p

(
X
)

C_p(X)

of continuous real-valued functions on

X
X

with the pointwise convergence topology does not admit a continuous bijection onto a

σ
\sigma

-compact space. This answers a question of Arhangel’skii.
Reanalysis of radial velocity data from the resonant planetary system HD128311
Authors: Rein Hanno
Published: January 2015

The multiplanetary system HD128311 hosts at least two planets. Its dynamical formation history has been studied extensively in the literature. We reanalyse the latest radial velocity data for this system with the affine-invariant Markov chain Monte Carlo sampler emcee. Using the high-order integrator IAS15, we perform a fully dynamical fit, allowing the planets to interact during the sampling process. A stability analysis using the Mean Exponential Growth of Nearby Orbits indicator reveals that the system is located in a stable island of the parameter space. In contrast to a previous study, we find that the system is locked in a 2:1 mean motion resonance. The resonant angle φ1 is librating with a libration amplitude of approximately 37°. The existence of mean motion resonances has important implication for planet formation theories. Our results confirm predictions of models involving planet migration and stochastic forces.
Primary and secondary siRNA synthesis triggered by RNAs from food bacteria in the ciliate Paramecium tetraurelia
Authors: Carradec Quentin , Götz Ulrike , Arnaiz Olivier , Pouch Juliette , Simon Martin , Meyer Eric , Marker Simone
Published: January 2015

In various organisms, an efficient RNAi response can be triggered by feeding cells with bacteria producing double-stranded RNA (dsRNA) against an endogenous gene. However, the detailed mechanisms and natural functions of this pathway are not well understood in most cases. Here, we studied siRNA biogenesis from exogenous RNA and its genetic overlap with endogenous RNAi in the ciliate Paramecium tetraurelia by high-throughput sequencing. Using wild-type and mutant strains deficient for dsRNA feeding we found that high levels of primary siRNAs of both strands are processed from the ingested dsRNA trigger by the Dicer Dcr1, the RNA-dependent RNA polymerases Rdr1 and Rdr2 and other factors. We further show that this induces the synthesis of secondary siRNAs spreading along the entire endogenous mRNA, demonstrating the occurrence of both 3′-to-5′ and 5′-to-3′ transitivity for the first time in the SAR clade of eukaryotes (Stramenopiles, Alveolates, Rhizaria). Secondary siRNAs depend on Rdr2 and show a strong antisense bias; they are produced at much lower levels than primary siRNAs and hardly contribute to RNAi efficiency. We further provide evidence that the Paramecium RNAi machinery also processes single-stranded RNAs from its bacterial food, broadening the possible natural functions of exogenously induced RNAi in this organism.
Development of a unique epigenetic signature during in vivo Th17 differentiation
Authors: Yang Bi-Huei , Floess Stefan , Hagemann Stefanie , Deyneko Igor V. , Groebe Lothar , Pezoldt Joern , Sparwasser Tim , Lochner Matthias , Huehn Jochen
Published: January 2015

Activated naive CD4+ T cells are highly plastic cells that can differentiate into various T helper (Th) cell fates characterized by the expression of effector cytokines like IFN-γ (Th1), IL-4 (Th2) or IL-17A (Th17). Although previous studies have demonstrated that epigenetic mechanisms including DNA demethylation can stabilize effector cytokine expression, a comprehensive analysis of the changes in the DNA methylation pattern during differentiation of naive T cells into Th cell subsets is lacking. Hence, we here performed a genome-wide methylome analysis of ex vivo isolated naive CD4+ T cells, Th1 and Th17 cells. We could demonstrate that naive CD4+ T cells share more demethylated regions with Th17 cells when compared to Th1 cells, and that overall Th17 cells display the highest number of demethylated regions, findings which are in line with the previously reported plasticity of Th17 cells. We could identify seven regions located in Il17a, Zfp362, Ccr6, Acsbg1, Dpp4, Rora and Dclk1 showing pronounced demethylation selectively in ex vivo isolated Th17 cells when compared to other ex vivo isolated Th cell subsets and in vitro generated Th17 cells, suggesting that this unique epigenetic signature allows identifying and functionally characterizing in vivo generated Th17 cells.
Mid-winter temperatures, not spring temperatures, predict breeding phenology in the European starlingSturnus vulgaris
Authors: Williams Tony D. , Bourgeon Sophie , Cornell Allison , Ferguson Laramie , Fowler Melinda , Fronstin Raime B. , Love Oliver P.
Published: January 2015

In many species, empirical data suggest that temperatures less than 1 month before breeding strongly influence laying date, consistent with predictions that short lag times between cue and response are more reliable, decreasing the chance of mismatch with prey. Here we show in European starlings (Sturnus vulgaris) that mid-winter temperatureca50–90 days before laying (8 January–22 February) strongly (r2= 0.89) predicts annual variation in laying date. Mid-winter temperature also correlated highly with relative clutch size: birds laid later, but laid larger clutches, in years when mid-winter temperatures were lower. Despite a high degree of breeding synchrony (mean laying date 5–13 April = ±4 days; 80% of nests laid within 4.8 days within year), European starlings show strong date-dependent variation in clutch size and productivity, but this appears to be mediated by a different temporal mechanism for integration of supplemental cue (temperature) information. We suggest the relationship between mid-winter temperature and breeding phenology might be indirect with both components correlating with a third factor: temperature-dependent development of the starling's insect (tipulid) prey. Mid-winter temperatures might set the trajectory of growth and final biomass of tipulid larvae, with this temperature cue providing starlings with information on breeding season prey availability (though exactlyhowremains unknown).
Building a responsive teacher: how temporal contingency of gaze interaction influences word learning with virtual tutors
Authors: Lee Hanju , Kanakogi Yasuhiro , Hiraki Kazuo
Published: January 2015

Animated pedagogical agents are lifelike virtual characters designed to augment learning. A review of developmental psychology literature led to the hypothesis that the temporal contingency of such agents would promote human learning. We developed a Pedagogical Agent with Gaze Interaction (PAGI), an experimental animated pedagogical agent that engages in gaze interaction with students. In this study, university students learned words of a foreign language, with temporally contingent PAGI (live group) or recorded version of PAGI (recorded group), which played pre-recorded sequences from live sessions. The result revealed that students in the live group scored considerably better than those in the recorded group. The finding indicates that incorporating temporal contingency of gaze interaction from a pedagogical agent has positive effect on learning.
Software for the analysis and visualization of deep mutational scanning data
Authors: Bloom Jesse D.
Published: January 2015

Background

Deep mutational scanning is a technique to estimate the impacts of mutations on a gene by using deep sequencing to count mutations in a library of variants before and after imposing a functional selection. The impacts of mutations must be inferred from changes in their counts after selection.

Results

I describe a software package,dms_tools, to infer the impacts of mutations from deep mutational scanning data using a likelihood-based treatment of the mutation counts. I show thatdms_toolsyields more accurate inferences on simulated data than simply calculating ratios of counts pre-and post-selection. Usingdms_tools, one can infer the preference of each site for each amino acid given a single selection pressure, or assess the extent to which these preferences change under different selection pressures. The preferences and their changes can be intuitively visualized with sequence-logo-style plots created using an extension toweblogo.

Conclusions

dms_toolsimplements a statistically principled approach for the analysis and subsequent visualization of deep mutational scanning data.
De novo Mutations in NALCN Cause a Syndrome of Congenital Contractures of the Limbs and Face with Hypotonia, and Developmental Delay
Authors: Chong Jessica X , McMillin Margaret J , Shively Kathryn M , Beck Anita E , Marvin Colby T , Armenteros Jose R , Buckingham Kati J , Nkinsi Naomi T , Boyle Evan A , Berry Margaret N , Bocian Maureen , Foulds Nicola , Giovannucci Uzielli Maria Luisa , Haldeman-Englert Chad , Hennekam Raoul CM , Kaplan Paige , Kline Antonie D , Mercer Catherine L , Nowaczyk Malgorzata JM , Klein Wassink-Ruiter Jolien S , McPherson Elizabeth W , Moreno Regina A , Scheuerle Angela E , Shashi Vandana , Stevens Cathy A , Carey John C , Monteil Arnaud , Lory Philippe , Tabor Holly K , Smith Joshua D , Shendure Jay , Nickerson Deborah A , Bamshad Michael J
Published: January 2015

Freeman-Sheldon syndrome, or distal arthrogryposis type 2A (DA2A), is an autosomal dominant condition caused by mutations in MYH3 and characterized by multiple congenital contractures of the face and limbs and normal cognitive development. We identified a subset of five simplex cases putatively diagnosed with “DA2A with severe neurological abnormalities” in which the proband had Congenital Contractures of the LImbs and FAce, Hypotonia, and global Developmental Delay often resulting in early death, a unique condition that we now refer to as CLIFAHDD syndrome. Exome sequencing identified missense mutations in sodium leak channel, nonselective (NALCN) in four families with CLIFAHDD syndrome. Using molecular inversion probes to screen NALCN in a cohort of 202 DA cases as well as concurrent exome sequencing of six other DA cases revealed NALCN mutations in ten additional families with “atypical” forms of DA. All fourteen mutations were missense variants predicted to alter amino acid residues in or near the S5 and S6 pore-forming segments of NALCN, highlighting the functional importance of these segments. In vitro functional studies demonstrated that mutant NALCN nearly abolished the expression of wildtype NALCN, suggesting that mutations that cause CLIFAHDD syndrome have a dominant negative effect. In contrast, homozygosity for mutations in other regions of NALCN has been reported in three families with an autosomal recessive condition characterized mainly by hypotonia and severe intellectual disability. Accordingly, mutations in NALCN can cause either a recessive or dominant condition with varied though overlapping phenotypic features perhaps depending on the type of mutation and affected protein domain(s).
ATDC induces an invasive switch in KRAS-induced pancreatic tumorigenesis
Authors: Wang Lidong , Yang Huibin , Abel Ethan V. , Ney Gina M. , Palmbos Phillip L. , Bednar Filip , Zhang Yaqing , Leflein Jacob , Waghray Meghna , Owens Scott , Wilkinson John E. , Prasad Jayendra , Ljungman Mats , Rhim Andrew D. , Pasca di Magliano Marina , Simeone Diane M.
Published: January 2015

The initiation of pancreatic ductal adenocarcinoma (PDA) is linked to activating mutations in KRAS. However, in PDA mouse models, expression of oncogenic mutant KRAS during development gives rise to tumors only after a prolonged latency or following induction of pancreatitis. Here we describe a novel mouse model expressing ataxia telangiectasia group D complementing gene (ATDC, also known as TRIM29 [tripartite motif 29]) that, in the presence of oncogenic KRAS, accelerates pancreatic intraepithelial neoplasia (PanIN) formation and the development of invasive and metastatic cancers. We found that ATDC up-regulates CD44 in mouse and human PanIN lesions via activation of β-catenin signaling, leading to the induction of an epithelial-to-mesenchymal transition (EMT) phenotype characterized by expression of Zeb1 and Snail1. We show that ATDC is up-regulated by oncogenic Kras in a subset of PanIN cells that are capable of invading the surrounding stroma. These results delineate a novel molecular pathway for EMT in pancreatic tumorigenesis, showing that ATDC is a proximal regulator of EMT.
From equator to pole: splitting chromosomes in mitosis and meiosis
Authors: Duro Eris , Marston Adèle L.
Published: January 2015

During eukaryotic cell division, chromosomes must be precisely partitioned to daughter cells. This relies on a mechanism to move chromosomes in defined directions within the parental cell. While sister chromatids are segregated from one another in mitosis and meiosis II, specific adaptations enable the segregation of homologous chromosomes during meiosis I to reduce ploidy for gamete production. Many of the factors that drive these directed chromosome movements are known, and their molecular mechanism has started to be uncovered. Here we review the mechanisms of eukaryotic chromosome segregation, with a particular emphasis on the modifications that ensure the segregation of homologous chromosomes during meiosis I.
A lacZ reporter gene expression atlas for 313 adult KOMP mutant mouse lines
Authors: West David B. , Pasumarthi Ravi K. , Baridon Brian , Djan Esi , Trainor Amanda , Griffey Stephen M. , Engelhard Eric K. , Rapp Jared , Li Bowen , Jong Pieter J. de , Lloyd K.C. Kent
Published: January 2015

Expression of the bacterial beta-galactosidase reporter gene (lacZ) in the vector used for the Knockout Mouse Project (KOMP) is driven by the endogenous promoter of the target gene. In tissues from KOMP mice, histochemical staining for LacZ enzyme activity can be used to determine gene expression patterns. With this technique, we have produced a comprehensive resource of gene expression using both whole mount (WM) and frozen section (FS) LacZ staining in 313 unique KOMP mutant mouse lines. Of these, ∼80% of mutants showed specific staining in one or more tissues, while ∼20% showed no specific staining, ∼13% had staining in only one tissue, and ∼25% had staining in >6 tissues. The highest frequency of specific staining occurred in the brain (∼50%), male gonads (42%), and kidney (39%). The WM method was useful for rapidly identifying whole organ and some substructure staining, while the FS method often revealed substructure and cellular staining specificity. Both staining methods had >90% repeatability in biological replicates. Nonspecific LacZ staining occurs in some tissues due to the presence of bacteria or endogenous enzyme activity. However, this can be effectively distinguished from reporter gene activity by the combination of the WM and FS methods. After careful annotation, LacZ staining patterns in a high percentage of mutants revealed a unique structure-function not previously reported for many of these genes. The validation of methods for LacZ staining, annotation, and expression analysis reported here provides unique insights into the function of genes for which little is currently known.
The amygdala is critical for trace, delay, and contextual fear conditioning
Authors: Kochli Daniel E. , Thompson Elaine C. , Fricke Elizabeth A. , Postle Abagail F. , Quinn Jennifer J.
Published: January 2015

Numerous investigations have definitively shown amygdalar involvement in delay and contextual fear conditioning. However, much less is known about amygdala contributions to trace fear conditioning, and what little evidence exists is conflicting as noted in previous studies. This discrepancy may result from selective targeting of individual nuclei within the amygdala. The present experiments further examine the contributions of amygdalar subnuclei to trace, delay, and contextual fear conditioning. Rats were trained using a 10-trial trace, delay, or unpaired fear conditioning procedure. Pretraining lesions targeting the entire basolateral amygdala (BLA) resulted in a deficit in trace, delay, and contextual fear conditioning. Immediate post-training infusions of the protein synthesis inhibitor, cycloheximide, targeting the basal nucleus of the amygdala (BA) attenuated trace and contextual fear memory expression, but had no effect on delay fear conditioning. However, infusions targeting the lateral nucleus of the amygdala (LA) immediately following conditioning attenuated contextual fear memory expression, but had no effect on delay or trace fear conditioning. In follow-up experiments, rats were trained using a three-trial delay conditioning procedure. Immediate post-training infusions targeting the LA produced deficits in both delay tone and context fear, while infusions targeting the BA produced deficits in context but not delay tone fear. These data fully support a role for the BLA in trace, delay, and contextual fear memories. Specifically, these data suggest that the BA may be more critical for trace fear conditioning, whereas the LA may be more critical for delay fear memories.
Effects of long-term representations on free recall of unrelated words
Authors: Katkov Mikhail , Romani Sandro , Tsodyks Misha
Published: January 2015

Human memory stores vast amounts of information. Yet recalling this information is often challenging when specific cues are lacking. Here we consider an associative model of retrieval where each recalled item triggers the recall of the next item based on the similarity between their long-term neuronal representations. The model predicts that different items stored in memory have different probability to be recalled depending on the size of their representation. Moreover, items with high recall probability tend to be recalled earlier and suppress other items. We performed an analysis of a large data set on free recall and found a highly specific pattern of statistical dependencies predicted by the model, in particular negative correlations between the number of words recalled and their average recall probability. Taken together, experimental and modeling results presented here reveal complex interactions between memory items during recall that severely constrain recall capacity.
The role of the basolateral amygdala in punishment
Authors: Jean-Richard-Dit-Bressel Philip , McNally Gavan P.
Published: January 2015

Aversive stimuli not only support fear conditioning to their environmental antecedents, they also punish behaviors that cause their occurrence. The amygdala, especially the basolateral nucleus (BLA), has been critically implicated in Pavlovian fear learning but its role in punishment remains poorly understood. Here, we used a within-subjects punishment task to assess the role of the BLA in the acquisition and expression of punishment as well as aversive choice. Rats that pressed two individually presented levers for pellet rewards rapidly suppressed responding to one lever if it also caused footshock deliveries (punished lever) but continued pressing a second lever that did not cause footshock (unpunished lever). Infusions of GABA agonists baclofen and muscimol (BM) into the BLA significantly impaired the acquisition of this suppression. BLA inactivations using BM also reduced the expression of well-trained punishment. There was anatomical segregation within the BLA so that caudal, not rostral, BLA was implicated in punishment. However, when presented with punished and unpunished levers simultaneously in a choice test without deliveries of shock punisher, rats expressed a preference for unpunished over the punished lever and BLA inactivations had no effect on this preference. Taken together, these findings indicate that the BLA is important for both the acquisition and expression of punishment but not for aversive choice. This role appears to be linked to neurons in the caudal BLA, rather than rostral BLA, although the circuitry that contributes to this functional segregation is currently unknown, and is most parsimoniously interpreted as a role for caudal BLA in determining the aversive value of the shock punisher.
Epac activation initiates associative odor preference memories in the rat pup
Authors: Grimes Matthew T. , Powell Maria , Gutierrez Sandra Mohammed , Darby-King Andrea , Harley Carolyn W. , McLean John H.
Published: January 2015

Here we examine the role of the exchange protein directly activated by cAMP (Epac) in β-adrenergic-dependent associative odor preference learning in rat pups. Bulbar Epac agonist (8-pCPT-2-O-Me-cAMP, or 8-pCPT) infusions, paired with odor, initiated preference learning, which was selective for the paired odor. Interestingly, pairing odor with Epac activation produced both short-term (STM) and long-term (LTM) odor preference memories. Training using β-adrenergic-activation paired with odor recruited rapid and transient ERK phosphorylation consistent with a role for Epac activation in normal learning. An ERK antagonist prevented intermediate-term memory (ITM) and LTM, but not STM. Epac agonist infusions induced ERK phosphorylation in the mitral cell layer, in the inner half of the dendritic external plexiform layer, in the glomeruli and, patchily, among granule cells. Increased CREB phosphorylation in the mitral and granule cell layers was also seen. Simultaneous blockade of both ERK and CREB pathways prevented any long-term β-adrenergic activated odor preference memory, while LTM deficits associated with blocking only one pathway were prevented by stronger β-adrenergic activation. These results suggest that Epac and PKA play parallel and independent, as well as likely synergistic, roles in creating cAMP-dependent associative memory in rat pups. They further implicate a novel ERK-independent pathway in the mediation of STM by Epac.