bluuebunny/crossref_metadata_2025 huggingface dataset:
SAT-based termination analysis using monotonicity constraints over the integers
Authors: CODISH MICHAEL , GONOPOLSKIY IGOR , BEN-AMRAM AMIR M. , FUHS CARSTEN , GIESL JÜRGEN
Published: July 2011

We describe an algorithm for proving termination of programs abstracted to systems of monotonicity constraints in the integer domain. Monotonicity constraints are a nontrivial extension of the well-known size-change termination method. While deciding termination for systems of monotonicity constraints is PSPACE complete, we focus on a well-defined and significant subset, which we call MCNP (for “monotonicity constraints in NP”), designed to be amenable to a SAT-based solution. Our technique is based on the search for a special type of ranking function defined in terms of bounded differences between multisets of integer values. We describe the application of our approach as the back end for the termination analysis of Java Bytecode. At the front end, systems of monotonicity constraints are obtained by abstracting information, using two different termination analyzers:AProVEandCOSTA. Preliminary results reveal that our approach provides a good trade-off between precision and cost of analysis.
Normative design using inductive learning
Authors: CORAPI DOMENICO , RUSSO ALESSANDRA , DE VOS MARINA , PADGET JULIAN , SATOH KEN
Published: July 2011

In this paper we propose a use-case-driven iterative design methodology for normative frameworks, also called virtual institutions, which are used to govern open systems. Our computational model represents the normative framework as a logic program under answer set semantics (ASP). By means of an inductive logic programming approach, implemented using ASP, it is possible to synthesise new rules and revise the existing ones. The learning mechanism is guided by the designer who describes the desired properties of the framework through use cases, comprising (i) event traces that capture possible scenarios, and (ii) a state that describes the desired outcome. The learning process then proposes additional rules, or changes to current rules, to satisfy the constraints expressed in the use cases. Thus, the contribution of this paper is a process for the elaboration and revision of a normative framework by means of a semi-automatic and iterative process driven from specifications of (un)desirable behaviour. The process integrates a novel and general methodology for theory revision based on ASP.
Entwicklung und Validierung der Trierer Kurzskala zur Messung von Work-Life Balance (TKS-WLB)
Authors: Syrek Christine , Bauer-Emmel Claudia , Antoni Conny , Klusemann Jens
Published: July 2011

Zusammenfassung. In diesem Beitrag wird die Trierer Kurzskala zur Messung von Work-Life Balance vorgestellt. Sie ermöglicht eine globale, richtungsfreie und in ihrem Aufwand ökonomische Möglichkeit zur Erfassung von Work-Life Balance. Die Struktur der Skala wurde anhand zweier Stichproben sowie einem zusätzlich erhobenen Fremdbild untersucht. Die Ergebnisse der Konstruktvalidierung bestätigten die einfaktorielle Struktur der Skala. Die interne Konsistenz der Skala erwies sich in beiden Studien als gut. Zudem konnte die empirische Trennbarkeit der Trierer Work-Life Balance Skala gegenüber einem gängigen Instrument zur Messung des Work-Family Conflicts ( Carlson, Kacmar & Williams, 2000 ) belegt werden. Im Hinblick auf die Kriteriumsvalidität der Skala wurden die angenommenen Zusammenhänge zu arbeits-, nicht-arbeits- sowie stressbezogenen Outcome-Variablen nachgewiesen. Die Eignung der Trierer Work-Life Balance Kurzskala zeigt sich auch daran, dass die Korrelationen zwischen den erhobenen Outcome-Variablen und dem Work-Family Conflict und denen der Trierer Work-Life Balance Skala ähnlich waren. Überdies vermochte die Trierer Work-Life Balance Skala über die Dimensionen des Work-Family Conflicts hinaus inkrementelle Varianz in den Outcome-Variablen aufzuklären. Insgesamt sprechen damit die Ergebnisse beider Stichproben für die Reliabilität und Validität der Trierer Work-Life Balance Kurzskala.
Formation of oil and gas intrusions after the Deepwater Horizon oil spill
Authors: Tretkoff Ernie
Published: July 2011

After the Deepwater Horizon oil spill in 2010, hydrocarbons were released into the Gulf of Mexico. These hydrocarbons were found to have formed large subsurface horizontal intrusions. Socolofsky et al. studied the dynamics of the formation of these intrusions, looking at observations from the Deepwater Horizon blowout, and adapted relationships developed from lab experiments to describe the mechanisms underlying the formation of the intrusions. The authors found that the intrusions form from density stratification of multiphase plumes containing dissolved gas and oil as well as small liquid drops. They developed a method for estimating intrusion elevation and found that their estimates agreed well with observations that the intrusions were primarily between 800 and 1200 meters in depth. The models could help researchers studying the fate of subsurface oil and gas. (Geophysical Research Letters, doi:10.1029/2011GL047174, 2011)
Calculating specific catchment area
Authors: Tretkoff Ernie
Published: July 2011

Specific catchment area, defined as the area of land upslope of a width of contour, divided by the contour width, is a commonly used quantity in hydrology to describe complex terrain for analyzing water flow on hill slopes; it can be a surrogate for water discharge per unit flow width. Although specific catchment area is important in hydrological, ecological, and geological studies, it can be difficult to estimate. Gallant and Hutchinson provide a simple differential equation that describes the rate of change of specific catchment area along a flow path. The equation can be directly integrated to calculate specific catchment area at any point on a digital elevation model. The method avoids use of catchment area and width estimates, which have errors. Although the method is more computationally intense than most methods for calculating specific catchment area, it can be used as a reference against which other methods can be tested. (Water Resources Research, doi:10.1029/2009WR008540, 2011)
Control of macrophage lineage populations by CSF‐1 receptor and GM‐CSF in homeostasis and inflammation
Authors: Lenzo Jason C , Turner Amanda L , Cook Andrew D , Vlahos Ross , Anderson Gary P , Reynolds Eric C , Hamilton John A
Published: July 2011

There is recent interest in the role of monocyte/macrophage subpopulations in pathology. How the hemopoietic growth factors, macrophage‐colony stimulating factor (M‐CSF or CSF‐1) and granulocyte macrophage (GM)‐CSF, regulate their in vivo development and function is unclear. A comparison is made here on the effect of CSF‐1 receptor (CSF‐1R) and GM‐CSF blockade/depletion on such subpopulations, both in the steady state and during inflammation. In the steady state, administration of neutralizing anti‐CSF‐1R monoclonal antibody (mAb) rapidly (within 3–4 days) lowered, specifically, the number of the more mature Ly6Clo peripheral blood murine monocyte population and resident peritoneal macrophages; it also reduced the accumulation of murine exudate (Ly6Clo) macrophages in two peritonitis models and alveolar macrophages in lung inflammation, consistent with a non‐redundant role for CSF‐1 (or interleukin‐34) in certain inflammatory reactions. A neutralizing mAb to GM‐CSF also reduced inflammatory macrophage numbers during antigen‐induced peritonitis and lung inflammation. In GM‐CSF gene‐deficient mice, a detailed kinetic analysis of monocyte/macrophage and neutrophil dynamics in antigen‐induced peritonitis suggested that GM‐CSF was acting, in part, systemically to maintain the inflammatory reaction. A model is proposed in which CSF‐1R signaling controls the development of the macrophage lineage at a relatively late stage under steady state conditions and during certain inflammatory reactions, whereas in inflammation, GM‐CSF can be required to maintain the response by contributing to the prolonged extravasation of immature monocytes and neutrophils. A correlation has been observed between macrophage numbers and the severity of certain inflammatory conditions, and it could be that CSF‐1 and GM‐CSF contribute to the control of these numbers in the ways proposed.
Working With Older Adults: Impact of the Affordable Care Act and Other Trends in Health Care
Authors: Hasselkus Amy
Published: July 2011

Rapidly increasing numbers in our aging population coupled with anticipated changes in reimbursement and health-care delivery have led to policy changes that will be implemented over time. This article will review the Patient Protection and Affordable Care Act of 2010 (ACA) and the Health Care and Education Reconciliation Act and will discuss the impact of health care changes on speech-language pathology practice with older adults.
Working With Resistance and Encouraging Buy-In to New Programs
Authors: Joffe Sara
Published: July 2011

In order to best meet the needs of older residents in long-term care settings, clinicians often develop programs designed to streamline and improve care. However, many individuals are reluctant to embrace change. This article will discuss strategies that the speech-language pathologist (SLP) can use to assess and address the source of resistance to new programs and thereby facilitate optimal outcomes.
From Reactive Intervention to Proactive Prevention: The Evolution of Occupational Dysphonia
Authors: Epstein Ruth , Remacle Angélique , Morsomme Dominique
Published: July 2011

Voice clinicians long have been aware of the concept of professional voice users: individuals who work in professions that have a higher incidence and increased risk for voice disorders. This realization, coupled with the documented impact of work-related dysphonia on the economy, has resulted in a growing international interest in developing occupational health benchmarks for voice use, similar to other standards developed for work-related factors such as noise-induced hearing loss. In this article, we review current perspectives and examine some issues related to occupational vocal health.
Lessons learned from the development and marketing of Mozilla Firefox 1.0
Authors: Jin Leigh , Robertson Bruce , Khoo Huoy Min
Published: July 2011

This case uses first-person sources to put the reader inside the teams that developed and marketed the Firefox browser. A brief overview of the Open Source Software (OSS) development process and the various roles played by members of a software development community, as well as a brief summary of the browser wars of the 1990s that saw Netscape Navigator fall from the dominant browser in the market to a distant second place behind Microsoft's Internet Explorer, help provide context for the case. In order to adapt the OSS development model to support a consumer-oriented product, Firefox developers adopted four rules: ‘We want it to be small,’ ‘Let's not keep too many cooks,’ ‘All patches are not created equal,’ and ‘All users are not created equal.’ The development team established a goal of 10 million downloads in the first 100 days and a 10% market share in the first year as measures of success for the new browser. In order to compete with Microsoft in the browser market, the Firefox team needed to leverage the development community to reach millions of potential end users. By providing a web-based structure for collaboration, and through a series of top-down initiatives (providing marketing tools to the community), and bottom-up initiatives (receiving and disseminating marketing ideas from the community at large), the team was able to achieve its marketing goals. In so doing, the SpreadFirefox initiative created a marketing community with roles analogous to a software development community.
Investigating the luminescence properties as a function of activator concentration in single crystal cerium doped Lu2SiO5: Determination of the configuration coordinate model
Authors: Peak Jonathan D. , Melcher Charles L. , Rack Philip D.
Published: July 2011

The effect of cerium concentration on single crystal lutetium orthosilicate (Lu2SiO5, LSO) was investigated with temperature-dependent steady state and time resolved luminescence spectroscopy. The results were used to determine the thermal quenching activation energies and the phonon energies responsible for the thermal broadening of the luminescence spectra. The measured phonon values were used to calculate configuration coordinate (CC) diagrams of the luminescence centers. The nature of single crystal LSO:Ce concentration quenching was determined to be due to radiative energy transfer by self-absorption. The observed broadening of the excitation spectra and narrowing of the emission spectra with increasing cerium was explained via a CC model. A combination of the CC model and concentration quenching explained the measured thermal quenching activation energies.
Enhanced 2.7 μm emission and energy transfer mechanism of Nd3+/Er3+ co-doped sodium tellurite glasses
Authors: Guo Yanyan , Li Ming , Tian Ying , Xu Rongrong , Hu Lili , Zhang Junjie
Published: July 2011

2.7 μm emission properties and energy transfer mechanism of Nd3+/Er3+ co-doped sodium tellurite glasses are investigated in present paper. Absorption and emission spectra were tested to characterize the 2.7 μm emission properties of Nd3+/Er3+ co-doped sodium tellurite glasses and a reasonable energy transfer mechanism of 2.7 μm emission between Er3+ and Nd3+ ions was proposed. Intense 2.7 μm emission was obtained from Nd3+/Er3+ co-doped sodium tellurite glasses due to the efficient energy transfer from Nd3+ to Er3+ ions under 808 nm LD pumping. Meanwhile, strongly decreased 545 nm up-conversion and 1.5 μm emissions were observed. Additionally, to obtain efficient 2.7 μm emission, the optimized concentration ratio of Nd3+ to Er3+ was found to be 0.5:1 in present glass system. Our results suggest that the present Nd3+/Er3+ co-doped sodium tellurite glass might have potential application in mid-infrared lasers.
Numerical analysis of plasma evolution on dielectric barrier discharge plasma actuator
Authors: Nishida Hiroyuki , Abe Takashi
Published: July 2011

Time evolution of the discharge plasma in the dielectric barrier discharge (DBD) plasma actuator was simulated by the simple fluid model in which the electron and single positive ion species were considered. The characteristics of the discharge plasma evolution were investigated in detail, and the following results were obtained. When the positive-going voltage is applied, the streamer discharge is formed periodically. The periodically formed streamer expands from the exposed electrode, and its length becomes longer than the previous one. Periodic breakdown of the gas and step-by-step plasma expansion are also observed during the negative-going voltage; however, the streamer is not formed and the breakdown frequency is much higher. The simulation results with a triangular applied voltage waveform show the same characteristics as observed in the experiment; large discharge current spikes are observed during both the positive- and negative-going voltage phase, and the plasma in the negative-going voltage phase expands more smoothly than that in the positive phase because of its higher breakdown frequency. It was shown that even the simple numerical model could provide valuable insights into the physics of DBD plasma actuator; this indicates that the positive ions and electrons play a prominent role in determining the general characteristics of the plasma evolution.
Large reversible magnetocaloric effect in La0.7-xPrxCa0.3MnO3
Authors: Rebello A. , Naik V. B. , Mahendiran R.
Published: July 2011

We report magnetocaloric effect in polycrystalline La0.7−xPrxCa0.3MnO3 (x = 0.0, 0.25, 0.3, 0.35, 0.4, and 0.45) samples. The magnetic entropy change (ΔSm) was measured using a differential scanning calorimeter (DSC) working in a magnetic field environment. The ΔSm shows a peak around the ferromagnetic Curie temperature (TC), and the magnitude of the peak decreases with increasing x (ΔSm = 8.15, 7.27, 6.92, 6.73, 6.41, and 5.84 Jkg−1K−1 for x = 0, 0.25, 0.3, 0.35, 0.4, and 0.45, respectively, for a field change of ΔH = 5 T). We have studied electrical, magnetoresistance, and magnetic properties of x = 0.35 compound in detail. The paramagnetic-ferromagnetic transition in this compound is found to be first order in nature. Magnetization isotherms show a field-induced metamagnetic transition in the paramagnetic (PM) state, and it is accompanied by a change in latent heat, as evidenced by the DSC data. Magnetization data give ΔSm = −7.09 Jkg−1K−1 at T = 190 K and a relative cooling power of 306.5 Jkg−1 for ΔH = 5 T in x = 0.35. We suggest that nanometer sized ferromagnetic clusters are pre-formed in the PM state above TC, and they coexist with short-range charge-orbital-ordered (COO) clusters in zero H field for x > 0. The observed large magnetocaloric effect with negligible hysteresis in M-H is associated with the metamagnetic transition resulting from the destruction of the COO clusters and growth of ferromagnetic clusters in size. The existence of significant ΔSm values over a wide composition makes this series interesting for magnetic refrigeration in the temperature range T = 100 K-270 K.
Toward a better understanding of the nanoscale degradation mechanisms of ultra-thin Si02/Si films: Investigation of the best experimental conditions with a conductive-atomic force microscope
Authors: Arinero R. , Hourani W. , Touboul A. D. , Gautier B. , Ramonda M. , Albertini D. , Militaru L. , Gonzalez-Velo Y. , Guasch C. , Saigné F.
Published: July 2011

We report, in this paper, investigations on the experimental conditions to be adopted to improve the reproducibility and the stability of conductive-atomic force microscopy experiments performed on ultra-thin oxide films. In particular, we demonstrate the key role of the water film layer which can disturb the acquisition of ramp voltage stresses and, in fine, lead to an important tip oxidation. Starting from these results, Weibull statistical analyses of stress-induced electrical degradation were carried out under vacuum on SiO2/Si films. We studied the influence of different parameters like the oxide thickness, the substrate doping type and doping level. We also observed important morphological effects, more or less visible, according to the type of tip and the oxide thickness. Those effects can be attributed, on one hand, to different temperature rise at the tip/oxide interface and, on the other hand, to different energy dissipated through the oxide film.
Formation of sheet plumes, current coils, and helical magnetic fields in a spherical magnetohydrodynamic dynamo
Authors: Miyagoshi Takehiro , Kageyama Akira , Sato Tetsuya
Published: July 2011

Aiming at understanding of magnetic field generation process in rapidly rotating stars and planets represented by the Earth, computer simulations of magnetohydrodynamic (MHD) dynamo were performed in a rotating spherical shell geometry. Thermal convection and dynamo process with Ekman number of the order of 10−7 were studied. New structures of convection motion, dynamo-generated electrical current, and magnetic field are found. The flow is organized as a set of thin, sheet-like plumes. The current is made of small-scale coil structure with magnetic flux tubes within each of the coil. These flux tubes are connected each other to form a large scale helical magnetic field structure.
Investigation of effect of excitation frequency on electron energy distribution functions in low pressure radio frequency bounded plasmas
Authors: Bhattacharjee Sudeep , Lafleur Trevor , Charles Christine , Boswell Rod
Published: July 2011

Particle in cell (PIC) simulations are employed to investigate the effect of excitation frequency ω on electron energy distribution functions (EEDFs) in a low pressure radio frequency (rf) discharge. The discharge is maintained over a length of 0.10 m, bounded by two infinite parallel plates, with the coherent heating field localized at the center of the discharge over a distance of 0.05 m and applied perpendicularly along the y and z directions. On varying the excitation frequency f (=ω/2π) in the range 0.01–50 MHz, it is observed that for f ≤ 5 MHz the EEDF shows a trend toward a convex (Druyvesteyn-like) distribution. For f > 5 MHz, the distribution resembles more like a Maxwellian with the familiar break energy visible in most of the distributions. A prominent “hot tail” is observed at f ≥ 20 MHz and the temperature of the tail is seen to decrease with further increase in frequency (e.g., at 30 MHz and 50 MHz). The mechanism for the generation of the “hot tail” is considered to be due to preferential transit time heating of energetic electrons as a function of ω, in the antenna heating field. There exists an optimum frequency for which high energy electrons are maximally heated. The occurrence of the Druyvesteyn-like distributions at lower ω may be explained by a balance between the heating of the electrons in the effective electric field and elastic cooling due to electron neutral collision frequency νen; the transition being dictated by ω ∼ 2πνen.
Identifying catalyst in Li-N-H system by x-ray absorption spectroscopy
Authors: Isobe Shigehito , Hino Satoshi , Ichikawa Takayuki , Kojima Yoshitsugu
Published: July 2011

Chemical bonding states of titanium compounds in LiH and LiNH2 mixture, which have been a candidate for a hydrogen storage material, have been examined by x-ray absorption spectroscopy measurement as the characterization of the catalysts. The results of x-ray absorption near-edge structure indicated that the Ti atoms in the Ti compounds, which had the catalytic effect on the kinetics of the hydrogen desorption properties, had a common electronic (chemical bonding) state. Additionally, this common electronic state of the Ti catalysts agrees with that of TiCl3·5NH3. These results indicated that TiCl3·5NH3 could act as the catalyst.
The flexible non-volatile memory devices using oxide semiconductors and ferroelectric polymer poly(vinylidene fluoride-trifluoroethylene)
Authors: Lee Gwang-Geun , Tokumitsu Eisuke , Yoon Sung-Min , Fujisaki Yoshihisa , Yoon Joo-Won , Ishiwara Hiroshi
Published: July 2011

We demonstrated flexible ferroelectric gate thin-film transistors (Fe-TFTs) with ferroelectric polymer poly(vinylidene fluoride-trifluoroethylene) [P(VDF-TrFE)] and amorphous indium gallium zinc oxide (a-IGZO) channel on the polyethylene-naphthalate (PEN) substrate. First, we confirm basic ferroelectric properties of the P(VDF-TrFE) film on the PEN substrate with various bending radius. Next, we fabricated Fe-TFTs with Al/120 nm-P(VDF-TrFE)/40 nm-IGZO top gate structure. Excellent electrical characteristics are demonstrated and nonvolatile memory function was confirmed with a memory window of 8.4 V. A subthreshold voltage swing of 400 mV/decade, Ion/Ioff ratio of more than 107 and the field-effect mobility of ∼1 cm2/Vs were obtained.
Signature of electron-phonon interaction in high temperature superconductors
Authors: Ashokan Vinod , Indu B. D. , Dimri A. Kr.
Published: July 2011

The theory of thermal conductivity of high temperature superconductors (HTS) based on electron and phonon line width (life times) formulation is developed with Quantum dynamical approach of Green's function. The frequency line width is observed as an extremely sensitive quantity in the transport phenomena of HTS as a collection of large number of scattering processes. The role of resonance scattering and electron-phonon interaction processes is found to be most prominent near critical temperature. The theory successfully explains the spectacular behaviour of high Tc superconductors in the vicinity of transition temperature. A successful agreement between theory and experiment has been obtained by analyzing the thermal conductivity data for the sample La1.8Sr0.2CuO4 in the temperature range 0 − 200K. The theory is equally and successfully applicable to all other high Tc superconductors.
Maintenance of tumor initiating cells of defined genetic composition by nucleostemin
Authors: Okamoto Naoko , Yasukawa Mami , Nguyen Christine , Kasim Vivi , Maida Yoshiko , Possemato Richard , Shibata Tatsuhiro , Ligon Keith L. , Fukami Kiyoko , Hahn William C. , Masutomi Kenkichi
Published: July 2011

Recent work has identified a subset of cells resident in tumors that exhibit properties similar to those found in normal stem cells. Such cells are highly tumorigenic and may be involved in resistance to treatment. However, the genes that regulate the tumor initiating cell (TIC) state are unknown. Here, we show that overexpression of either of the nucleolar GTP-binding proteins nucleostemin (NS) or GNL3L drives the fraction of genetically defined tumor cells that exhibit markers and tumorigenic properties of TICs. Specifically, cells that constitutively express elevated levels of NS or GNL3L exhibit increased TWIST expression, phosphorylation of STAT3, expression of genes that induce pluripotent stem cells, and enhanced radioresistance; in addition, they form tumors even when small numbers of cells are implanted and exhibit an increased propensity to metastasize. GNL3L/NS forms a complex with the telomerase catalytic subunit [human telomerase reverse transcriptase (hTERT)] and the SWItch-Sucrose NonFermentable (SWI-SNF) complex protein brahma-related gene 1 (BRG1), and the expression of each of these components is necessary to facilitate the cancer stem cell state. Together, these observations define a complex composed of TERT, BRG1, and NS/GNL3L that maintains the function of TICs.
A regulatory gene induces trichome formation and embryo lethality in tomato
Authors: Yang Changxian , Li Hanxia , Zhang Junhong , Luo Zhidan , Gong Pengjuan , Zhang Chanjuan , Li Jinhua , Wang Taotao , Zhang Yuyang , Lu Yong'en , Ye Zhibiao
Published: July 2011

Trichomes are universal biological structures originating from the aerial epidermis, which serve as an excellent model to study plant differentiation at the cell level. Although the pathway regulating trichome formation in the Rosids has been well characterized, only very recently a few genes were identified for trichome initiation in the Asterids. In this study, we cloned
Woolly
(
Wo
), essential for trichome formation in tomato. Transgenic experiments revealed that the woolly phenotype is caused by the mutation in
Wo
which encodes a homeodomain protein containing a bZIP motif and a START domain. We identified three alleles of
Wo
and found that each allele contains a missense mutation, which respectively results in an amino acid substitution at the C terminus. Microarray and expression analysis showed that the expression of a B-type cyclin gene,
SlCycB2
, is possibly regulated by
Wo
, which also participates in trichome formation. Suppression of
Wo
or
SlCycB2
expression by RNAi decreased the number of type I trichomes, and direct protein–protein interaction was detected between them, implying that both proteins may work together in the regulation of this type of trichome formation. Cytological observation and
Wo
transcript analysis in the developing seeds showed that embryo development was also correlated with
Wo
.
Hydrodynamic property of the cytoplasm is sufficient to mediate cytoplasmic streaming in the
Caenorhabiditis elegans
embryo
Authors: Niwayama Ritsuya , Shinohara Kyosuke , Kimura Akatsuki
Published: July 2011

Cytoplasmic streaming is a type of intracellular transport widely seen in nature. Cytoplasmic streaming in
Caenorhabditis elegans
at the one-cell stage is bidirectional; the flow near the cortex (“cortical flow”) is oriented toward the anterior, whereas the flow in the central region (“cytoplasmic flow”) is oriented toward the posterior. Both cortical flow and cytoplasmic flow depend on non-muscle-myosin II (NMY-2), which primarily localizes in the cortex. The manner in which NMY-2 proteins drive cytoplasmic flow in the opposite direction from remote locations has not been fully understood. In this study, we demonstrated that the hydrodynamic properties of the cytoplasm are sufficient to mediate the forces generated by the cortical myosin to drive bidirectional streaming throughout the cytoplasm. We quantified the flow velocities of cytoplasmic streaming using particle image velocimetry (PIV) and conducted a three-dimensional hydrodynamic simulation using the moving particle semiimplicit method. Our simulation quantitatively reconstructed the quantified flow velocity distribution resolved through PIV analysis. Furthermore, our PIV analyses detected microtubule-dependent flows during the pronuclear migration stage. These flows were reproduced via hydrodynamic interactions between moving pronuclei and the cytoplasm. The agreement of flow dynamics in vivo and in simulation indicates that the hydrodynamic properties of the cytoplasm are sufficient to mediate cytoplasmic streaming in
C. elegans
embryos.
Multidisciplinary perspectives on banana (
Musa
spp.) domestication
Authors: Perrier Xavier , De Langhe Edmond , Donohue Mark , Lentfer Carol , Vrydaghs Luc , Bakry Frédéric , Carreel Françoise , Hippolyte Isabelle , Horry Jean-Pierre , Jenny Christophe , Lebot Vincent , Risterucci Ange-Marie , Tomekpe Kodjo , Doutrelepont Hugues , Ball Terry , Manwaring Jason , de Maret Pierre , Denham Tim
Published: July 2011

Original multidisciplinary research hereby clarifies the complex geodomestication pathways that generated the vast range of banana cultivars (cvs). Genetic analyses identify the wild ancestors of modern-day cvs and elucidate several key stages of domestication for different cv groups. Archaeology and linguistics shed light on the historical roles of people in the movement and cultivation of bananas from New Guinea to West Africa during the Holocene. The historical reconstruction of domestication processes is essential for breeding programs seeking to diversify and improve banana cvs for the future.
Crystal structures of
λ
exonuclease in complex with DNA suggest an electrostatic ratchet mechanism for processivity
Authors: Zhang Jinjin , McCabe Kimberly A. , Bell Charles E.
Published: July 2011

The
λ
exonuclease is an ATP-independent enzyme that binds to dsDNA ends and processively digests the 5′-ended strand to form 5′ mononucleotides and a long 3′ overhang. The crystal structure of
λ
exonuclease revealed a toroidal homotrimer with a central funnel-shaped channel for tracking along the DNA, and a mechanism for processivity based on topological linkage of the trimer to the DNA was proposed. Here, we have determined the crystal structure of
λ
exonuclease in complex with DNA at 1.88-Å resolution. The structure reveals that the enzyme unwinds the DNA prior to cleavage, such that two nucleotides of the 5′-ended strand insert into the active site of one subunit of the trimer, while the 3′-ended strand passes through the central channel to emerge out the back of the trimer. Unwinding of the DNA is facilitated by several apolar residues, including Leu78, that wedge into the base pairs at the single/double-strand junction to form favorable hydrophobic interactions. The terminal 5′ phosphate of the DNA binds to a positively charged pocket buried at the end of the active site, while the scissile phosphate bridges two active site Mg
2+
ions. Our data suggest a mechanism for processivity in which wedging of Leu78 and other apolar residues into the base pairs of the DNA restricts backward movement, whereas attraction of the 5′ phosphate to the positively charged pocket drives forward movement of the enzyme along the DNA at each cycle of the reaction. Thus, processivity of
λ
exonuclease operates not only at the level of the trimer, but also at the level of the monomer.
Interhomolog recombination and loss of heterozygosity in wild-type and Bloom syndrome helicase (BLM)-deficient mammalian cells
Authors: LaRocque Jeannine R. , Stark Jeremy M. , Oh Jin , Bojilova Ekaterina , Yusa Kosuke , Horie Kyoji , Takeda Junji , Jasin Maria
Published: July 2011

Genomic integrity often is compromised in tumor cells, as illustrated by genetic alterations leading to loss of heterozygosity (LOH). One mechanism of LOH is mitotic crossover recombination between homologous chromosomes, potentially initiated by a double-strand break (DSB). To examine LOH associated with DSB-induced interhomolog recombination, we analyzed recombination events using a reporter in mouse embryonic stem cells derived from F1 hybrid embryos. In this study, we were able to identify LOH events although they occur only rarely in wild-type cells (≤2.5%). The low frequency of LOH during interhomolog recombination suggests that crossing over is rare in wild-type cells. Candidate factors that may suppress crossovers include the RecQ helicase deficient in Bloom syndrome cells (BLM), which is part of a complex that dissolves recombination intermediates. We analyzed interhomolog recombination in BLM-deficient cells and found that, although interhomolog recombination is slightly decreased in the absence of BLM, LOH is increased by fivefold or more, implying significantly increased interhomolog crossing over. These events frequently are associated with a second homologous recombination event, which may be related to the mitotic bivalent structure and/or the cell-cycle stage at which the initiating DSB occurs.
Structural basis for alcohol modulation of a pentameric ligand-gated ion channel
Authors: Howard Rebecca J. , Murail Samuel , Ondricek Kathryn E. , Corringer Pierre-Jean , Lindahl Erik , Trudell James R. , Harris R. Adron
Published: July 2011

Despite its long history of use and abuse in human culture, the molecular basis for alcohol action in the brain is poorly understood. The recent determination of the atomic-scale structure of GLIC, a prokaryotic member of the pentameric ligand-gated ion channel (pLGIC) family, provides a unique opportunity to characterize the structural basis for modulation of these channels, many of which are alcohol targets in brain. We observed that GLIC recapitulates bimodal modulation by
n
-alcohols, similar to some eukaryotic pLGICs: methanol and ethanol weakly potentiated proton-activated currents in GLIC, whereas
n
-alcohols larger than ethanol inhibited them. Mapping of residues important to alcohol modulation of ionotropic receptors for glycine, γ-aminobutyric acid, and acetylcholine onto GLIC revealed their proximity to transmembrane cavities that may accommodate one or more alcohol molecules. Site-directed mutations in the pore-lining M2 helix allowed the identification of four residues that influence alcohol potentiation, with the direction of their effects reflecting α-helical structure. At one of the potentiation-enhancing residues, decreased side chain volume converted GLIC into a highly ethanol-sensitive channel, comparable to its eukaryotic relatives. Covalent labeling of M2 positions with an alcohol analog, a methanethiosulfonate reagent, further implicated residues at the extracellular end of the helix in alcohol binding. Molecular dynamics simulations elucidated the structural consequences of a potentiation-enhancing mutation and suggested a structural mechanism for alcohol potentiation via interaction with a transmembrane cavity previously termed the “linking tunnel.” These results provide a unique structural model for independent potentiating and inhibitory interactions of
n
-alcohols with a pLGIC family member.
Architecture of the high mobility group nucleosomal protein 2-nucleosome complex as revealed by methyl-based NMR
Authors: Kato Hidenori , van Ingen Hugo , Zhou Bing-Rui , Feng Hanqiao , Bustin Michael , Kay Lewis E. , Bai Yawen
Published: July 2011

Chromatin structure and function are regulated by numerous proteins through specific binding to nucleosomes. The structural basis of many of these interactions is unknown, as in the case of the high mobility group nucleosomal (HMGN) protein family that regulates various chromatin functions, including transcription. Here, we report the architecture of the HMGN2-nucleosome complex determined by a combination of methyl-transverse relaxation optimized nuclear magnetic resonance spectroscopy (methyl-TROSY) and mutational analysis. We found that HMGN2 binds to both the acidic patch in the H2A-H2B dimer and to nucleosomal DNA near the entry/exit point, “stapling” the histone core and the DNA. These results provide insight into how HMGNs regulate chromatin structure through interfering with the binding of linker histone H1 to the nucleosome as well as a structural basis of how phosphorylation induces dissociation of HMGNs from chromatin during mitosis. Importantly, our approach is generally applicable to the study of nucleosome-binding interactions in chromatin.
Childbearing impeded education more than education impeded childbearing among Norwegian women
Authors: Cohen Joel E. , Kravdal Øystein , Keilman Nico
Published: July 2011

In most societies, women at age 39 with higher levels of education have fewer children. To understand this association, we investigated the effects of childbearing on educational attainment and the effects of education on fertility in the 1964 birth cohort of Norwegian women. Using detailed annual data from ages 17 to 39, we estimated the probabilities of an additional birth, a change in educational level, and enrollment in the coming year, conditional on fertility history, educational level, and enrollment history at the beginning of each year. A simple model reproduced a declining gradient of children ever born with increasing educational level at age 39. When a counterfactual simulation assumed no effects of childbearing on educational progression or enrollment (without changing the estimated effects of education on childbearing), the simulated number of children ever born decreased very little with increasing completed educational level, contrary to data. However, when another counterfactual simulation assumed no effects of current educational level and enrollment on childbearing (without changing the estimated effects of childbearing on education), the simulated number of children ever born decreased with increasing completed educational level nearly as much as the decrease in the data. In summary, in these Norwegian data, childbearing impeded education much more than education impeded childbearing. These results suggest that women with advanced degrees have lower completed fertility on the average principally because women who have one or more children early are more likely to leave or not enter long educational tracks and never attain a high educational level.
Compatibility of H9N2 avian influenza surface genes and 2009 pandemic H1N1 internal genes for transmission in the ferret model
Authors: Kimble J. Brian , Sorrell Erin , Shao Hongxia , Martin Philip L. , Perez Daniel Roberto
Published: July 2011

In 2009, a novel H1N1 influenza (pH1N1) virus caused the first influenza pandemic in 40 y. The virus was identified as a triple reassortant between avian, swine, and human influenza viruses, highlighting the importance of reassortment in the generation of viruses with pandemic potential. Previously, we showed that a reassortant virus composed of wild-type avian H9N2 surface genes in a seasonal human H3N2 backbone could gain efficient respiratory droplet transmission in the ferret model. Here we determine the ability of the H9N2 surface genes in the context of the internal genes of a pH1N1 virus to efficiently transmit via respiratory droplets in ferrets. We generated reassorted viruses carrying the HA gene alone or in combination with the NA gene of a prototypical H9N2 virus in the background of a pH1N1 virus. Four reassortant viruses were generated, with three of them showing efficient respiratory droplet transmission. Differences in replication efficiency were observed for these viruses; however, the results clearly indicate that H9N2 avian influenza viruses and pH1N1 viruses, both of which have occasionally infected pigs, have the potential to reassort and generate novel viruses with respiratory transmission potential in mammals.
CNS expression of glucocerebrosidase corrects α-synuclein pathology and memory in a mouse model of Gaucher-related synucleinopathy
Authors: Sardi S. Pablo , Clarke Jennifer , Kinnecom Cathrine , Tamsett Thomas J. , Li Lingyun , Stanek Lisa M. , Passini Marco A. , Grabowski Gregory A. , Schlossmacher Michael G. , Sidman Richard L. , Cheng Seng H. , Shihabuddin Lamya S.
Published: July 2011

Emerging genetic and clinical evidence suggests a link between Gaucher disease and the synucleinopathies Parkinson disease and dementia with Lewy bodies. Here, we provide evidence that a mouse model of Gaucher disease (

Gba1
D409V/D409V

) exhibits characteristics of synucleinopathies, including progressive accumulation of proteinase K-resistant α-synuclein/ubiquitin aggregates in hippocampal neurons and a coincident memory deficit. Analysis of homozygous (

Gba1
D409V/D409V

) and heterozygous (

Gba1
D409V/+

and

Gba1
+/−

) Gaucher mice indicated that these pathologies are a result of the combination of a loss of glucocerebrosidase activity and a toxic gain-of-function resulting from expression of the mutant enzyme. Importantly, adeno-associated virus-mediated expression of exogenous glucocerebrosidase injected into the hippocampus of

Gba1
D409V/D409V

mice ameliorated both the histopathological and memory aberrations. The data support the contention that mutations in
GBA1
can cause Parkinson disease-like α-synuclein pathology, and that rescuing brain glucocerebrosidase activity might represent a therapeutic strategy for
GBA1
-associated synucleinopathies.
Ipl1/Aurora-dependent phosphorylation of Sli15/INCENP regulates CPC–spindle interaction to ensure proper microtubule dynamics
Authors: Nakajima Yuko , Cormier Anthony , Tyers Randall G. , Pigula Adrianne , Peng Yutian , Drubin David G. , Barnes Georjana
Published: July 2011

Dynamic microtubules facilitate chromosome arrangement before anaphase, whereas during anaphase microtubule stability assists chromosome separation. Changes in microtubule dynamics at the metaphase–anaphase transition are regulated by Cdk1. Cdk1-mediated phosphorylation of Sli15/INCENP promotes preanaphase microtubule dynamics by preventing chromosomal passenger complex (CPC; Sli15/INCENP, Bir1/Survivin, Nbl1/Borealin, Ipl1/Aurora) association with spindles. However, whether Cdk1 has sole control over microtubule dynamics, and how CPC–microtubule association influences microtubule behavior, are unclear. Here, we show that Ipl1/Aurora-dependent phosphorylation of Sli15/INCENP modulates microtubule dynamics by preventing CPC binding to the preanaphase spindle and to the central spindle until late anaphase, facilitating spatiotemporal control of microtubule dynamics required for proper metaphase centromere positioning and anaphase spindle elongation. Decreased Ipl1-dependent Sli15 phosphorylation drives direct CPC binding to microtubules, revealing how the CPC influences microtubule dynamics. We propose that Cdk1 and Ipl1/Aurora cooperatively modulate microtubule dynamics and that Ipl1/Aurora-dependent phosphorylation of Sli15 controls spindle function by excluding the CPC from spindle regions engaged in microtubule polymerization.
Cytoplasmic γ-actin and tropomodulin isoforms link to the sarcoplasmic reticulum in skeletal muscle fibers
Authors: Gokhin David S. , Fowler Velia M.
Published: July 2011

The sarcoplasmic reticulum (SR) serves as the Ca2+ reservoir for muscle contraction. Tropomodulins (Tmods) cap filamentous actin (F-actin) pointed ends, bind tropomyosins (Tms), and regulate F-actin organization. In this paper, we use a genetic targeting approach to examine the effect of Tmod1 deletion on the organization of cytoplasmic γ-actin (γcyto-actin) in the SR of skeletal muscle. In wild-type muscle fibers, γcyto-actin and Tmod3 defined an SR microdomain that was distinct from another Z line–flanking SR microdomain containing Tmod1 and Tmod4. The γcyto-actin/Tmod3 microdomain contained an M line complex composed of small ankyrin 1.5 (sAnk1.5), γcyto-actin, Tmod3, Tm4, and Tm5NM1. Tmod1 deletion caused Tmod3 to leave its SR compartment, leading to mislocalization and destabilization of the Tmod3–γcyto-actin–sAnk1.5 complex. This was accompanied by SR morphological defects, impaired Ca2+ release, and an age-dependent increase in sarcomere misalignment. Thus, Tmod3 regulates SR-associated γcyto-actin architecture, mechanically stabilizes the SR via a novel cytoskeletal linkage to sAnk1.5, and maintains the alignment of adjacent myofibrils.
POM121 and Sun1 play a role in early steps of interphase NPC assembly
Authors: Talamas Jessica A. , Hetzer Martin W.
Published: July 2011

Nuclear pore complexes (NPCs) assemble at the end of mitosis during nuclear envelope (NE) reformation and into an intact NE as cells progress through interphase. Although recent studies have shown that NPC formation occurs by two different molecular mechanisms at two distinct cell cycle stages, little is known about the molecular players that mediate the fusion of the outer and inner nuclear membranes to form pores. In this paper, we provide evidence that the transmembrane nucleoporin (Nup), POM121, but not the Nup107–160 complex, is present at new pore assembly sites at a time that coincides with inner nuclear membrane (INM) and outer nuclear membrane (ONM) fusion. Overexpression of POM121 resulted in juxtaposition of the INM and ONM. Additionally, Sun1, an INM protein that is known to interact with the cytoskeleton, was specifically required for interphase assembly and localized with POM121 at forming pores. We propose a model in which POM121 and Sun1 interact transiently to promote early steps of interphase NPC assembly.
Tissue-specific expression of B7x protects from CD4 T cell–mediated autoimmunity
Authors: Wei Joyce , Loke P’ng , Zang Xingxing , Allison James P.
Published: July 2011

B7x, an inhibitory member of the B7/CD28 superfamily, is highly expressed in a broad range of nonhematopoietic organs, suggesting a role in maintaining peripheral tolerance. As endogenous B7x protein is expressed in pancreatic islets, we investigated whether the molecule inhibits diabetogenic responses. Transfer of disease-inducing BDC2.5 T cells into B7x-deficient mice resulted in a more aggressive form of diabetes than in wild-type animals. This exacerbation of disease correlated with higher frequencies of islet-infiltrating Th1 and Th17 cells. Conversely, local B7x overexpression inhibited the development of autoimmunity, as crossing diabetes-susceptible BDC2.5/B6g7 mice to animals overexpressing B7x in pancreatic islets abrogated disease induction. This protection was caused by the inhibition of IFN-γ production by CD4 T cells and not to a skewing or expansion of Th2 or regulatory T cells. The suppressive function of B7x was also supported by observations from another autoimmune model, experimental autoimmune encephalomyelitis, in which B7x-deficient mice developed exacerbated disease in comparison with wild-type animals. Analysis of central nervous system–infiltrating immune cells revealed that the loss of endogenous B7x resulted in expanded Th1 and Th17 responses. Data from these two autoimmune models provide evidence that B7x expression in the periphery acts as an immune checkpoint to prevent tissue-specific autoimmunity.