bluuebunny/crossref_metadata_2025 huggingface dataset:
A thin rivulet or ridge subject to a uniform transverse shear stress at its free surface due to an external airflow
Authors: Sullivan J. M. , Paterson C. , Wilson S. K. , Duffy B. R.
Published: August 2012

We use the lubrication approximation to analyze three closely related problems involving a thin rivulet or ridge (i.e., a two-dimensional droplet) of fluid subject to a prescribed uniform transverse shear stress at its free surface due to an external airflow, namely a rivulet draining under gravity down a vertical substrate, a rivulet driven by a longitudinal shear stress at its free surface, and a ridge on a horizontal substrate, and find qualitatively similar behaviour for all three problems. We show that, in agreement with previous numerical studies, the free surface profile of an equilibrium rivulet/ridge with pinned contact lines is skewed as the shear stress is increased from zero, and that there is a maximum value of the shear stress beyond which no solution with prescribed semi-width is possible. In practice, one or both of the contact lines will de-pin before this maximum value of the shear stress is reached, and so we consider situations in which the rivulet/ridge de-pins at one or both contact lines. In the case of de-pinning only at the advancing contact line, the rivulet/ridge is flattened and widened as the shear stress is increased from its critical value, and there is a second maximum value of the shear stress beyond which no solution with a prescribed advancing contact angle is possible. In contrast, in the case of de-pinning only at the receding contact line, the rivulet/ridge is thickened and narrowed as the shear stress is increased from its critical value, and there is a solution with a prescribed receding contact angle for all values of the shear stress. In general, in the case of de-pinning at both contact lines there is a critical “yield” value of the shear stress beyond which no equilibrium solution is possible and the rivulet/ridge will evolve unsteadily. In the Appendix, we show that an equilibrium rivulet/ridge with prescribed flux/area is quasi-statically stable to two-dimensional perturbations.
Particle size dependence of resonant-tunneling effect induced by CdS nanoparticles in a poly(N-vinylcarbazole) polymer matrix
Authors: Nenna Giuseppe , Masala Silvia , Bizzarro Valentina , Re Marilena , Pesce Emanuela , Minarini Carla , Di Luccio Tiziana
Published: August 2012

CdS nanoparticles of different sizes were synthesised in poly(N-vinylcarbazole) and studied in device structures glass/indium tin oxide (ITO)/PVK:CdS/Al. Electrical bistability and negative differential resistance (NDR) effects were observed in the current-voltage characteristics. In addition, the devices showed a considerable enhancement of the current magnitude. A dependence of the current conduction on the nanoparticle size and size distribution in the polymer was studied through electrical impedance measurements. The study revealed the importance of the charge effects of the nanoparticles resulting in a bistable behavior. A resonant tunneling current model was proposed to explain the NDR and its relation with the nanoparticle size and size distribution.
Impact fragmentation of aluminum reactive materials
Authors: Hooper Joseph P.
Published: August 2012

We report the fragmentation of brittle, granular aluminum spheres following high velocity impact (0.5-2.0 km/s) on thin steel plates. These spheres, machined from isostatically pressed aluminum powder, represent a prototypical metallic reactive material. The fragments generated by the impacts are collected in a soft-catch apparatus and analyzed down to a length scale of 44μm. With increasing velocity, there is a transition from an exponential Poisson-process fragment distribution with a characteristic length scale to a power-law behavior indicative of scale-invariance. A normalized power-law distribution with a finite size cutoff is introduced and used to analyze the number and mass distributions of the recovered fragments. At high impact velocities, the power-law behavior dominates the distribution and the power-law exponent is identical to the universal value for brittle fragmentation discussed in recent works. The length scale at which the power-law behavior decays is consistent with the idea that the length of side microbranches or damage zones from primary cracks is governing this cutoff. The transition in fragment distribution at high strain-rates also implies a significant increase in small fragments that can rapidly combust in an ambient atmosphere.
Exploding solutions of the complex two-dimensional Burgers equations: Computer simulations
Authors: Boldrighini C. , Frigio S. , Maponi P.
Published: August 2012

We study by computer simulations the complex solutions of the two-dimensional Burgers equations in the whole plane in absence of external forces. For such model the existence of singularities, corresponding to a divergence of the total energy at a finite time, is proved by Li and Sinai [“Singularities of complex-valued solutions of the two-dimensional Burgers system,” J. Math. Phys. 51, 015205 (2010)]10.1063/1.3276099 for a large class of initial data. The simulations show that the blow-up takes place in a very short time, of the order of 10−5 time units. Moreover near the blow-up time the support of the solution in Fourier space moves out to infinity along a straight line. In x-space the solutions are concentrated in a finite region, with large space derivatives, as one would expect for physical phenomena such as tornadoes.
Phase coherence and attractor geometry of chaotic electrochemical oscillators
Authors: Zou Yong , Donner Reik V. , Wickramasinghe Mahesh , Kiss István Z. , Small Michael , Kurths Jürgen
Published: August 2012

Chaotic attractors are known to often exhibit not only complex dynamics but also a complex geometry in phase space. In this work, we provide a detailed characterization of chaotic electrochemical oscillations obtained experimentally as well as numerically from a corresponding mathematical model. Power spectral density and recurrence time distributions reveal a considerable increase of dynamic complexity with increasing temperature of the system, resulting in a larger relative spread of the attractor in phase space. By allowing for feasible coordinate transformations, we demonstrate that the system, however, remains phase-coherent over the whole considered parameter range. This finding motivates a critical review of existing definitions of phase coherence that are exclusively based on dynamical characteristics and are thus potentially sensitive to projection effects in phase space. In contrast, referring to the attractor geometry, the gradual changes in some fundamental properties of the system commonly related to its phase coherence can be alternatively studied from a purely structural point of view. As a prospective example for a corresponding framework, recurrence network analysis widely avoids undesired projection effects that otherwise can lead to ambiguous results of some existing approaches to studying phase coherence. Our corresponding results demonstrate that since temperature increase induces more complex chaotic chemical reactions, the recurrence network properties describing attractor geometry also change gradually: the bimodality of the distribution of local clustering coefficients due to the attractor’s band structure disappears, and the corresponding asymmetry of the distribution as well as the average path length increase.
Organic/inorganic hybrid pn-junction between copper phthalocyanine and CdSe quantum dot layers as solar cells
Authors: Saha Sudip K. , Guchhait Asim , Pal Amlan J.
Published: August 2012

We have introduced an organic/inorganic hybrid pn-junction for solar cell applications. Layers of II-VI quantum dots and a metal-phthalocyanine in sequence have been used as n- and p-type materials, respectively, to form a junction. The film of quantum dots has been formed through a layer-by-layer process by replacing the long-chain ligands of the nanoparticles in each ultrathin layer or a monolayer with short-chain ones so that interparticle distance becomes small leading to a decrease in resistance of the quantum dot layer. With indium tin oxide and Au as electrodes, we have formed an inverted sandwiched structure. These electrodes formed ohmic contacts with the neighboring materials. From the current-voltage characteristics of the hybrid heterostructure, we have inferred formation of a depletion region at the pn-junction that played a key role in charge separation and correspondingly a photocurrent in the external circuit. For comparison, we have also formed and characterized Schottky devices based on components of the pn-junction keeping the electrode combination same. From capacitance-voltage characteristics, we have observed that the depletion region of the hybrid pn-junction was much wider as compared to that in Schottky devices based on components of the junction.
Diffusion-emission theory of photon enhanced thermionic emission solar energy harvesters
Authors: Varpula Aapo , Prunnila Mika
Published: August 2012

Numerical and semi-analytical models are presented for photon-enhanced-thermionic-emission (PETE) devices. The models take diffusion of electrons, inhomogeneous photogeneration, and bulk and surface recombination into account. The efficiencies of PETE devices with silicon cathodes are calculated. Our model predicts significantly different electron affinity and temperature dependence for the device than the earlier model based on a rate-equation description of the cathode. We show that surface recombination can reduce the efficiency below 10% at the cathode temperature of 800 K and the concentration of 1000 suns, but operating the device at high injection levels can increase the efficiency to 15%.
Flux-pinning-induced interfacial shearing and transverse normal stress in a superconducting coated conductor long strip
Authors: Jing Ze , Yong Huadong , Zhou Youhe
Published: August 2012

In this paper, a theoretical model is proposed to analyze the transverse normal stress and interfacial shearing stress induced by the electromagnetic force in the superconducting coated conductor. The plane strain approach is used and a singular integral equation is derived. By assuming that the critical current density is magnetic field independent and the superconducting film is infinitely thin, the interfacial shearing stress and normal stress in the film are evaluated for the coated conductor during the increasing and decreasing in the transport current, respectively. The calculation results are discussed and compared for the conductor with different substrate and geometry. The results indicate that the coated conductor with stiffer substrate and larger width experiences larger interfacial shearing stress and less normal stress in the film.
Safe timing for an urgent Caesarean section: what is the evidence to guide policy?
Authors: Homer Caroline S. E. , Catling-Paull Christine
Published: August 2012

Objective.
To determine, from the evidence, what is the optimum decision to delivery (DDI) intervals in emergency Caesarean sections (CS). The aim of the study was to help guide policy in maternity services and identify issues relating to DDI and safe practice in maternity care.

Method.
A systematic review of the literature was undertaken. Assessment of the quality of eligible papers was undertaken using the Critical Appraisal Skills Program (CASP) rating.

Results.
There is no strong evidence that a DDI of 30 min or less is associated with improved outcomes for babies or mothers. Some evidence suggests that a DDI of greater than 30 min but less than 75 min confers benefit, but these findings were confounded by the indications for the emergency CS.

Conclusion.
Urgent CS should occur as soon as possible, but there is insufficient evidence to support a definite time frame, such as 30 min. A consistency of approach and nomenclature in describing the urgency of CS is necessary, which would enable criteria for further audit regarding DDI. Staff training should be addressed to improve transfer systems for CS. Antenatal risk assessment and congruence with role delineation and service delivery capacity is important.

What is known about the topic?
The 30-min rule has been cited and used globally as best practice, despite the low level of supporting evidence.

What does this paper add?
There is no strong evidence that DDIs of less than 30 min are associated with improved neonatal or maternal outcomes. A DDI of greater than 30 min but less than 75 min confers some benefit, but this is tempered by the urgency of the CS.

What are the implications for practitioners?
Urgent CS should occur as soon as possible, but there is insufficient evidence to support a definite time frame, such as 30 min. A consistency of approach and nomenclature in describing the urgency of CS is necessary, which would enable criteria for further audit regarding DDI. Staff training should be addressed regarding efficient systems during transfer for CS. Careful antenatal risk assessment and congruence with role delineation and service delivery capacity is important in making recommendations for place of birth for women.
Rural Undergraduate Support and Coordination, Rural Clinical School, and Rural Australian Medical Undergraduate Scholarship: rural undergraduate initiatives and subsequent rural medical workforce
Authors: Playford Denese E. , Cheong Edwina
Published: August 2012

Background. This study examined postgraduate work after an undergraduate clinical year spent in the Rural Clinical School of Western Australia (RCSWA), compared with 6 weeks Rural Undergraduate Support and Coordination (RUSC)-funded rural experience in a 6-year undergraduate medical course. Rural background, sex and Rural Australian Medical Undergraduate Scholarship (RAMUS)-holding were taken into account. Methods. University of Western Australia undergraduate data were linked by hand with postgraduate placements to provide a comprehensive dataset on the rural exposure history of junior medical practitioners working in Western Australia between 2004 and 2007. Results. Participation in the RCSWA program was associated with significantly more postgraduate year one rural work than RUSC placement alone (OR = 1.5, CI 0.97–2.38). The RCSWA workforce effect increased at postgraduate year two (OR = 3.0, CI 1.6484 to 5.5935 relative to RUSC). Rural-origin practitioners who chose the RCSWA program were more likely than other rural-origin practitioners to take rural rotations in both postgraduate years. RAMUS holders’ choice in relation to the RCSWA program predicted later rural work. There were no effects of sex. Conclusions. Rural initiatives, in particular the Rural Clinical School program, are associated with postgraduate rural choices. The real impact of these data rely on the translation of early postgraduate choices into long-term work commitments. What is known about the topic? Specific training of rural graduates is strongly related to subsequent rural workforce. In addition, rural educational placements affect medical students’ intentions to practise rurally. Retrospective data from rural relative to urban general practitioners link rural background, rural undergraduate experience and rural postgraduate experience with rural work. What does this paper add? Much of the Australian prospective outcomes research has looked at workforce intentions of graduates, or the workforce outcomes of small graduate cohorts of Rural Clinical Schools. This paper followed nearly 500 graduates by name through to their PGY1 and PGY2 workforce decisions. As this cohort comprised 80% of three completely graduated MBBS years, these data validly represent the outcome of a medical school which is comparable to all Australian medical schools in its RUSC, Rural Clinical School and RAMUS recipients. The paper provides the first peer-reviewed outcomes data for the RAMUS scholarship program. What are the implications for practitioners? Rural supervision of medical students is an effective way to recruit new workforce. The longer students are supervised in rural settings, the better. But undergraduate programs need to be linked with postgraduate initiatives that take graduates of medical student initiatives into vocational programs able to deliver a trained rural workforce.
The effect of performance context and skill level on the frequency of flow experiences
Authors: Koehn Stefan , Morris Tony
Published: August 2012

The main purpose of this study was to examine interaction effects between skill level and performance contexts on the experience of flow in adolescent tennis players. The study employed a factorial design to examine differences in flow frequency between competition and training settings and the independent groups factor of ranking list and club players. Junior tennis players (55 males, 29 females) completed the Dispositional Flow Scale‐2 in training and competition settings. A repeated‐measure ANCOVA, with years of tennis experience and training hours per week as covariates, showed a significant main effect for skill level, F(1, 82) = 6.67, p<0.05, , a significant main effect for performance contexts, F(1, 82) = 7.69, p<0.01, , and a significant disordinal interaction, F(1, 82) = 9.93, p<0.01, . Lower skilled athletes experienced flow with similar frequency across performance contexts, whereas advanced players experienced flow more often during training than competition. Qualitative results showed that club players’ involvement in both performance contexts was mainly based on intrinsic reasons, whereas ranking list players reported intrinsic reasons for training, but a high number of extrinsic reasons for competition. Future studies should take propositions of the flow model into account in order to advance theoretical developments on interaction effects and shed more light into the complex processes underlying flow in sport.
Language dominance in translation priming: Evidence from balanced and unbalanced Chinese–English bilinguals
Authors: Wang Xin
Published: August 2012

It is well established in the masked translation priming literature that the priming effect is sensitive to language direction with noncognates—namely, the priming effect is consistently observed from first language (L1) to second language (L2), but not always from L2 to L1. Several recent reports demonstrated both L1–L2 and L2–L1 priming and attributed the restoration of L2–L1 priming to high proficiency in L2. Here, the current study tested two groups of highly proficient Chinese–English bilinguals, with one group more dominant in English and the other more balanced in both languages. The L2–L1 priming effect was only observed with the balanced bilinguals, but not the English-dominant ones. Based on these results, I argue that the language proficiency account is not sufficient to explain the priming asymmetry and that the relative bilingual balance is a more accurate account. Theoretically, the cross-language balance is determined by the representational difference between L1 and L2 at the semantic level. I discuss the results in relation to various bilingual models, in particular, the sense model and the distributional representational model (DRM), which capture the semantic representations of bilinguals.
A note on the convergence to initial data of heat and Poisson equations
Authors: Hartzstein Silvia , Torrea José , Viviani Beatriz
Published: August 2012

We characterize the weighted Lebesgue spaces,

L
p

(

R

n

,
v
(
x
)
d
x
)
,

L^p(\mathbb {R}^n,v(x)dx),

for which the solutions of the Heat and Poisson problems have limits a.e. when the time

t
t

tends to zero.
Ergosterol content specifies targeting of tail-anchored proteins to mitochondrial outer membranes
Authors: Krumpe Katrin , Frumkin Idan , Herzig Yonatan , Rimon Nitzan , Özbalci Cagakan , Brügger Britta , Rapaport Doron , Schuldiner Maya
Published: August 2012

Tail-anchored (TA) proteins have a single C-terminal transmembrane domain, making their biogenesis dependent on posttranslational translocation. Despite their importance, no dedicated insertion machinery has been uncovered for mitochondrial outer membrane (MOM) TA proteins. To decipher the molecular mechanisms guiding MOM TA protein insertion, we performed two independent systematic microscopic screens in which we visualized the localization of model MOM TA proteins on the background of mutants in all yeast genes. We could find no mutant in which insertion was completely blocked. However, both screens demonstrated that MOM TA proteins were partially localized to the endoplasmic reticulum (ER) in ∆spf1 cells. Spf1, an ER ATPase with unknown function, is the first protein shown to affect MOM TA protein insertion. We found that ER membranes in ∆spf1 cells become similar in their ergosterol content to mitochondrial membranes. Indeed, when we visualized MOM TA protein distribution in yeast strains with reduced ergosterol content, they phenocopied the loss of Spf1. We therefore suggest that the inherent differences in membrane composition between organelle membranes are sufficient to determine membrane integration specificity in a eukaryotic cell.
Actin-capping protein promotes microtubule stability by antagonizing the actin activity of mDia1
Authors: Bartolini Francesca , Ramalingam Nagendran , Gundersen Gregg G.
Published: August 2012

In migrating fibroblasts, RhoA and its effector mDia1 regulate the selective stabilization of microtubules (MTs) polarized in the direction of migration. The conserved formin homology 2 domain of mDia1 is involved both in actin polymerization and MT stabilization, and the relationship between these two activities is unknown. We found that latrunculin A (LatA) and jasplakinolide, actin drugs that release mDia1 from actin filament barbed ends, stimulated stable MT formation in serum-starved fibroblasts and caused a redistribution of mDia1 onto MTs. Knockdown of mDia1 by small interfering RNA (siRNA) prevented stable MT induction by LatA, whereas blocking upstream Rho or integrin signaling had no effect. In search of physiological regulators of mDia1, we found that actin-capping protein induced stable MTs in an mDia1-dependent manner and inhibited the translocation of mDia on the ends of growing actin filaments. Knockdown of capping protein by siRNA reduced stable MT levels in proliferating cells and in starved cells stimulated with lysophosphatidic acid. These results show that actin-capping protein is a novel regulator of MT stability that functions by antagonizing mDia1 activity toward actin filaments and suggest a novel form of actin–MT cross-talk in which a single factor acts sequentially on actin and MTs.
APCFZR1prevents nondisjunction in mouse oocytes by controlling meiotic spindle assembly timing
Authors: Holt Janet E. , Lane Simon I. R. , Jennings Phoebe , García-Higuera Irene , Moreno Sergio , Jones Keith T.
Published: August 2012

FZR1 is an anaphase-promoting complex (APC) activator best known for its role in the mitotic cell cycle at M-phase exit, in G1, and in maintaining genome integrity. Previous studies also established that it prevents meiotic resumption, equivalent to the G2/M transition. Here we report that mouse oocytes lacking FZR1 undergo passage through meiosis I that is accelerated by ∼1 h, and this is due to an earlier onset of spindle assembly checkpoint (SAC) satisfaction and APCCDC20activity. However, loss of FZR1 did not compromise SAC functionality; instead, earlier SAC satisfaction was achieved because the bipolar meiotic spindle was assembled more quickly in the absence of FZR1. This novel regulation of spindle assembly by FZR1 led to premature bivalent attachment to microtubules and loss of kinetochore-bound MAD2. Bivalents, however, were observed to congress poorly, leading to nondisjunction rates of 25%. We conclude that in mouse oocytes FZR1 controls the timing of assembly of the bipolar spindle and in so doing the timing of SAC satisfaction and APCCDC20activity. This study implicates FZR1 as a major regulator of prometaphase whose activity helps to prevent chromosome nondisjunction.
Regulation of the formin Bnr1 by septins anda MARK/Par1-family septin-associated kinase
Authors: Buttery Shawnna M. , Kono Keiko , Stokasimov Ema , Pellman David
Published: August 2012

Formin-family proteins promote the assembly of linear actin filaments and are required to generate cellular actin structures, such as actin stress fibers and the cytokinetic actomyosin contractile ring. Many formin proteins are regulated by an autoinhibition mechanism involving intramolecular binding of a Diaphanous inhibitory domain and a Diaphanous autoregulatory domain. However, the activation mechanism for these Diaphanous-related formins (DRFs) is not completely understood. Although small GTPases play an important role in relieving autoinhibition, other factors likely contribute. Here we describe a requirement for the septin Shs1 and the septin-associated kinase Gin4 for the localization and in vivo activity of the budding yeast DRF Bnr1. In budding yeast strains in which the other formin, Bni1, is conditionally inactivated, the loss of Gin4 or Shs1 results in the loss of actin cables and cell death, similar to the loss of Bnr1. The defects in these strains can be suppressed by constitutive activation of Bnr1. Gin4 is involved in both the localization and activation of Bnr1, whereas the septin Shs1 is required for Bnr1 activation but not its localization. Gin4 promotes the activity of Bnr1 independently of the Gin4 kinase activity, and Gin4 lacking its kinase domain binds to the critical localization region of Bnr1. These data reveal novel regulatory links between the actin and septin cytoskeletons.
Multiple protein kinases influence the redistribution of fission yeast Clp1/Cdc14 phosphatase upon genotoxic stress
Authors: Broadus Matthew R. , Gould Kathleen L.
Published: August 2012

The Cdc14 phosphatase family antagonizes Cdk1 phosphorylation and is important for mitotic exit. To access their substrates, Cdc14 phosphatases are released from nucleolar sequestration during mitosis. Clp1/Flp1, the Schizosaccharomyces pombe Cdc14 orthologue, and Cdc14B, a mammalian orthologue, also exit the nucleolus during interphase upon DNA replication stress or damage, respectively, implicating Cdc14 phosphatases in the response to genotoxic insults. However, a mechanistic understanding of Cdc14 phosphatase nucleolar release under these conditions is incomplete. We show here that relocalization of Clp1 during genotoxic stress is governed by complex phosphoregulation. Specifically, the Rad3 checkpoint effector kinases Cds1 and/or Chk1, the cell wall integrity mitogen-activated protein kinase Pmk1, and the cell cycle kinase Cdk1 directly phosphorylate Clp1 to promote genotoxic stress–induced nucleoplasmic accumulation. However, Cds1 and/or Chk1 phosphorylate RxxS sites preferentially upon hydroxyurea treatment, whereas Pmk1 and Cdk1 preferentially phosphorylate Clp1 TP sites upon H2O2treatment. Abolishing both Clp1 RxxS and TP phosphosites eliminates any genotoxic stress–induced redistribution. Reciprocally, preventing dephosphorylation of Clp1 TP sites shifts the distribution of the enzyme to the nucleoplasm constitutively. This work advances our understanding of pathways influencing Clp1 localization and may provide insight into mechanisms controlling Cdc14B phosphatases in higher eukaryotes.
Dynactin's pointed-end complex is a cargo-targeting module
Authors: Yeh Ting-Yu , Quintyne Nicholas J. , Scipioni Brett R. , Eckley D. Mark , Schroer Trina A.
Published: August 2012

Dynactin is an essential part of the cytoplasmic dynein motor that enhances motor processivity and serves as an adaptor that allows dynein to bind cargoes. Much is known about dynactin's interaction with dynein and microtubules, but how it associates with its diverse complement of subcellular binding partners remains mysterious. It has been suggested that cargo specification involves a group of subunits referred to as the “pointed-end complex.” We used chemical cross-linking, RNA interference, and protein overexpression to characterize interactions within the pointed-end complex and explore how it contributes to dynactin's interactions with endomembranes. The Arp11 subunit, which caps one end of dynactin's Arp1 filament, and p62, which binds Arp11 and Arp1, are necessary for dynactin stability. These subunits also allow dynactin to bind the nuclear envelope prior to mitosis. p27 and p25, by contrast, are peripheral components that can be removed without any obvious impact on dynactin integrity. Dynactin lacking these subunits shows reduced membrane binding. Depletion of p27 and p25 results in impaired early and recycling endosome movement, but late endosome movement is unaffected, and mitotic spindles appear normal. We conclude that the pointed-end complex is a bipartite structural domain that stabilizes dynactin and supports its binding to different subcellular structures.
Anillin-related protein Mid1p coordinates the assembly of the cytokinetic contractile ring in fission yeast
Authors: Saha Shambaditya , Pollard Thomas D.
Published: August 2012

In fission yeast cells cortical nodes containing the protein Blt1p and several kinases appear early in G2, mature into cytokinetic nodes by adding anillin Mid1p, myosin-II, formin Cdc12p, and other proteins, and condense into a contractile ring by movements that depend on actin and myosin-II. Previous studies concluded that cells without Mid1p lack cytokinetic nodes and assemble rings unreliably from myosin-II strands but left open questions. Why do strands form outside the equatorial region? Why is ring assembly unreliable without Mid1p? We found in Δmid1 cells that Cdc12p accumulates in cytokinetic nodes scattered in the cortex and produces actin filaments that associate with myosin-II, Rng2p, and Cdc15p to form strands located between the nodes. Strands incorporate nodes, and in ∼67% of cells, strands slowly close into rings that constrict without the normal ∼25-min maturation period. Ring assembly is unreliable and slow without Mid1p because the scattered Cdc12p nodes generate strands spread widely beyond the equator, and growing strands depend on random encounters to merge with other strands into a ring. We conclude that orderly assembly of the contractile ring in wild-type cells depends on Mid1p to recruit myosin-II, Rng2p, and Cdc15p to nodes and to place cytokinetic nodes around the cell equator.
Characterization of structural and functional domains of the anillin-related protein Mid1p that contribute to cytokinesis in fission yeast
Authors: Saha Shambaditya , Pollard Thomas D.
Published: August 2012

Fission yeast cells depend on the anillin-related protein Mid1p for reliable cytokinesis. Insolubility limits the purification of full-length Mid1p for biophysical analysis, and lack of knowledge about the structural domains of Mid1p limits functional analysis. We addressed these limitations by identifying in a bacterial expression screen of random Mid1p fragments five soluble segments that can be purified and one insoluble segment. Using complementation experiments in Δmid1 cells, we tested the biological functions of these six putative domains that account for full-length Mid1p. The N-terminal domain (residues 1–149) is essential for correct positioning and orientation of septa. The third domain (residues 309–452) allows the construct composed of the first three domains (residues 1-452) to form hydrodynamically well-behaved octamers. Constructs consisting of residues 1–452 or 1–578 carry out most functions of full-length Mid1p, including concentration at the equatorial cortex in nodes that accumulate myosin-II and other contractile ring proteins during mitosis. However, cells depending on these constructs without the insoluble domain (residues 579–797) form equatorially located rings slowly from strands rather than by direct condensation of nodes. We conclude that residues 1–578 assemble node components myosin-II, Rng2p, and Cdc15p, and the insoluble domain facilitates the normal, efficient condensation of nodes into rings.
Posterior Surgery for Adolescent Idiopathic Scoliosis With Pedicle Screws and Ultrahigh–Molecular Weight Polyethylene Tape
Authors: Imagama Shiro , Ito Zenya , Wakao Norimitsu , Ando Kei , Hirano Kenichi , Tauchi Ryoji , Muramoto Akio , Matsui Hiroki , Matsumoto Tomohiro , Sakai Yoshihito , Katayama Yoshito , Matsuyama Yukihiro , Ishiguro Naoki
Published: August 2012

Study Design:

Prospective clinical case series.

Objectives:

To describe our surgical procedure and results for posterior correction and fusion with a hybrid approach using pedicle screws, hooks, and ultrahigh–molecular weight polyethylene tape with direct vertebral rotation (DVR) (the PSTH-DVR procedure) for treatment of adolescent idiopathic scoliosis (AIS) with satisfactory correction in the coronal and sagittal planes.

Summary of Background Data:

Introduction of segmental pedicle screws in posterior surgery for AIS has facilitated good correction and fusion. However, procedures using only pedicle screws have risks during screw insertion, higher costs, and decreased postoperative thoracic kyphosis. We have obtained good outcomes compared with segmental pedicle screw fixation in surgery for AIS using a relatively simple operative procedure (PSTH-DVR) that uses fewer pedicle screws.

Methods:

The subjects were 30 consecutive patients with AIS who underwent the PSTH-DVR procedure and were followed for a minimum of 2 years. Preoperative flexibility, preoperative and postoperative Cobb angles, correction rates, loss of correction, thoracic kyphotic angles (T5–T12), coronal balance, sagittal balance, and shoulder balance were measured on plain radiographs. Rib hump, operation time, estimated blood loss, spinal cord monitoring findings, complications, and scoliosis research society (SRS)-22 scores were also examined.

Results:

The mean preoperative curve of 58.0 degrees (range, 40–96 degrees) was corrected to a mean of 9.9 degrees postoperatively, and the correction rate was 83.6%. Fusion was obtained in all patients without loss of correction. In 10 cases with preoperative kyphosis angles (T5–T12) <10 degrees, the preoperative mean of 5.8 degrees improved to 20.2 degrees at the final follow-up. Rib hump and coronal, sagittal and shoulder balances were also improved, and good SRS-22 scores were achieved at final follow-up.

Conclusions:

The correction of deformity with PSTH-DVR is equivalent to that of all-pedicle screw constructs. The procedure gives favorable correction, is advantageous for kyphosis compared with segmental screw fixation, and uses the minimum number of pedicle screws. Therefore, the PSTH-DVR procedure may be useful for treatment of idiopathic scoliosis.
Treatment of Early-Onset Spinal Deformity (EOSD) With VEPTR
Authors: Lattig Friederike , Taurman Rita , Hell Anna K.
Published: August 2012

Study Design:

Case Series.

Objective:

To describe the post-VEPTR (vertical expandable prosthetic titanium rib) treatment changes in early-onset spinal deformity (EOSD), which may influence the final correction spondylodesis.

Summary of Background Data:

The VEPTR device, originally developed for the treatment of congenital rib cage malformation, is nowadays more widely used in the treatment of EOSD. At present, only a few reports describe the possible complications that may occur with repeated lengthening procedures of the VEPTR, thereby making the final spondylodesis more complicated and less satisfactory.

Methods:

X-rays of 5 children treated for EOSD with 2 unilateral VEPTR (each rib to rib and rib to lumbar lamina) were analyzed for curve patterns and Cobb angles before, during, and at the end of VEPTR treatment, and after the final spondylodesis. Intraoperative observations during the spondylodesis, which influenced the possibilities of the curve correction, were documented.

Results:

All patients showed a marked decompensation of the frontal balance and a high degree of rigidity of the main curve and the compensatory curves after treatment with the VEPTR device. Because of this spontaneous autofusion of spinal segments, migration of the rib cradles and/or the laminar hook, and a change in the curve patterns, the final fusion had to be longer in all patients than the primary deformity would have intended.

Conclusions:

If an EOSD is treated with VEPTR, the curve progression and, in particular, the development of a high thoracic hyperkyphosis or rotation of the main curve should be critically observed. Autofusion of ribs and vertebral bodies may make the final correction spondylodesis even more challenging and risky for the patient and the end result less satisfactory.
PEEK Cages in Lumbar Fusion
Authors: Schimmel Janneke J. P. , Poeschmann Marcel S. , Horsting Philip P. , Schönfeld Dirk H. W. , van Limbeek Jacques , Pavlov Paul W.
Published: August 2012

Study Design:

Historical cohort analysis.

Objective:

Evaluation of mid-term clinical outcome and radiologic fusion in patients treated with a polyetheretherketone (PEEK) cage.

Summary of Background Data:

Anterior lumbar interbody fusion can be a good alternative in chronic low back pain when conservative treatment fails. Although titanium alloy cages give good fusion rates, disadvantages are the subsidence of the cage in the adjacent vertebrae and problematic radiologic evaluation of fusion. PEEK cages such as the Synfix-LR cage (Synthes, Switzerland) should overcome this.

Methods:

From December 2004 until August 2007, 95 patients (21 double-level and 74 single-level) with degenerative disk disease from L3–S1 were operated by a single surgeon. The number of reoperations was counted. Radiologic fusion on computed tomography scan was scored with a new scoring system by an independent skeletal radiologist and orthopedic surgeon. Intraobserver agreement and specificity were assessed. Clinical improvement was measured by the Oswestry Disability Index score. The median duration of clinical follow-up was 47.7 months (range 29.9–61.6).

Results:

In total, 26 patients were reoperated after a median period of 17.6 months (range 6.7–46.9) of the initial surgery. Of the 26 patients, 23 patients (18 single-level and 5 double-level) were reoperated for symptomatic pseudarthrosis. A moderate agreement (κ=0.36) and a specificity of 70% and 37% for the radiologist and orthopedic surgeon, respectively, were found for scoring bony bridging. The Oswestry Disability Index score improved after initial surgery; however, reoperated patients reported a significantly lower improvement.

Conclusions:

A high number of reoperations after an anterior lumbar interbody fusion procedure with the Synfix-LR cage were found, mainly because of symptomatic pseudarthrosis. The absence of posterior fixation in combination with lower stiffness and the hydrophobic characteristics of PEEK probably lead to insufficient initial stability, creating suboptimal conditions for bony bridging, and thus solid fusion. The proposed ease of the evaluation of radiologic fusion could not be supported. Clinicians should be alert on pseudarthrosis when patients treated with the Synfix-LR cage presented with persisted or aggravated complaints.
Malignant Peripheral Nerve Sheath Tumor
Authors: Tracy Jennifer A. , Rubin Devon I. , Amrami Kimberly K. , Spinner Robert J. , Engelstad JaNean K. , Scheithauer Bernd W. , Dyck P. James B.
Published: August 2012

We present the case of a 67-year-old man with a malignant peripheral nerve sheath tumor (MPNST) affecting the brachial plexus. He presented with progressive right upper extremity paresthesias, numbness, weakness, and severe pain. Nerve conduction studies/electromyography demonstrated a right lower and middle trunk predominant brachial plexopathy. Three-tesla magnetic resonance imaging of the brachial plexus showed a soft tissue mass with central necrosis and cystic changes and irregular contrast enhancement. Positron emission tomography showed increased fluorodeoxyglucose uptake within the mass. Targeted fascicular nerve biopsy revealed hypercellular tumor, featuring atypical cells with mitotic figures and limited immunoreactivity for S-100 protein. The findings were those of an MPNST. The effects on the variably involved fascicles were also seen in teased fiber preparations, paraffin sections, and through immunohistochemistry. This case illustrates the presentation of this rare type of tumor, and characteristic neuroimaging and pathologic features of MPNSTs.
Isolated Mononeuropathy Multiplex—A Rare Manifestation of Intravascular Large B-Cell Lymphoma
Authors: Lynch Karen M. , Katz Joshua D. , Weinberg David H. , Lin Douglas I. , Folkerth Rebecca D.
Published: August 2012

Intravascular large B-cell lymphoma, also known as angiotrophic large cell lymphoma, is a rare disorder where neoplastic lymphoid cells proliferate within the walls of small- to medium-sized blood vessels. Peripheral neuropathy and other neurological manifestations, including stroke and dementia, are common, but cases of isolated multiple mononeuropathies in the absence of systemic symptoms are distinctly rare. We present an unusual case of biopsy-proved angiotrophic large cell lymphoma presenting exclusively with multiple mononeuropathies.
Guthrie card methylomics identifies temporally stable epialleles that are present at birth in humans
Authors: Beyan Huriya , Down Thomas A. , Ramagopalan Sreeram V. , Uvebrant Kristina , Nilsson Anita , Holland Michelle L. , Gemma Carolina , Giovannoni Gavin , Boehm Bernhard O. , Ebers George C. , Lernmark Åke , Cilio Corrado M. , Leslie R. David , Rakyan Vardhman K.
Published: August 2012

A major concern in common disease epigenomics is distinguishing causal from consequential epigenetic variation. One means of addressing this issue is to identify the temporal origins of epigenetic variants via longitudinal analyses. However, prospective birth-cohort studies are expensive and time consuming. Here, we report DNA methylomics of archived Guthrie cards for the retrospective longitudinal analyses of in-utero-derived DNA methylation variation. We first validate two methodologies for generating comprehensive DNA methylomes from Guthrie cards. Then, using an integrated epigenomic/genomic analysis of Guthrie cards and follow-up samplings, we identify interindividual DNA methylation variation that is present both at birth and 3 yr later. These findings suggest that disease-relevant epigenetic variation could be detected at birth, i.e., before overt clinical disease. Guthrie card methylomics offers a potentially powerful and cost-effective strategy for studying the dynamics of interindividual epigenomic variation in a range of common human diseases.
Extensive compensatory cis-trans regulation in the evolution of mouse gene expression
Authors: Goncalves Angela , Leigh-Brown Sarah , Thybert David , Stefflova Klara , Turro Ernest , Flicek Paul , Brazma Alvis , Odom Duncan T. , Marioni John C.
Published: August 2012

Gene expression levels are thought to diverge primarily via regulatory mutations in trans within species, and in cis between species. To test this hypothesis in mammals we used RNA-sequencing to measure gene expression divergence between C57BL/6J and CAST/EiJ mouse strains and allele-specific expression in their F1 progeny. We identified 535 genes with parent-of-origin specific expression patterns, although few of these showed full allelic silencing. This suggests that the number of imprinted genes in a typical mouse somatic tissue is relatively small. In the set of nonimprinted genes, 32% showed evidence of divergent expression between the two strains. Of these, 2% could be attributed purely to variants acting in trans, while 43% were attributable only to variants acting in cis. The genes with expression divergence driven by changes in trans showed significantly higher sequence constraint than genes where the divergence was explained by variants acting in cis. The remaining genes with divergent patterns of expression (55%) were regulated by a combination of variants acting in cis and variants acting in trans. Intriguingly, the changes in expression induced by the cis and trans variants were in opposite directions more frequently than expected by chance, implying that compensatory regulation to stabilize gene expression levels is widespread. We propose that expression levels of genes regulated by this mechanism are fine-tuned by cis variants that arise following regulatory changes in trans, suggesting that many cis variants are not the primary targets of natural selection.
Romidepsin (FK228) and its analogs directly inhibit phosphatidylinositol 3‐kinase activity and potently induce apoptosis as histone deacetylase/phosphatidylinositol 3‐kinase dual inhibitors
Authors: Saijo Ken , Katoh Tadashi , Shimodaira Hideki , Oda Akifumi , Takahashi Ohgi , Ishioka Chikashi
Published: August 2012

Activation of phosphatidylinositol 3‐kinase (PI3K) signaling is involved in carcinogenesis and cancer progression. The PI3K inhibitors are considered candidate drugs for cancer treatment. Here, we describe a drug screening system for novel PI3K inhibitors using Saccharomyces cerevisiae strains with deleterious mutations in the ATP‐binding cassette transporter genes, because wild‐type S. cerevisiae uses drug efflux pumps for reducing intracellular drug concentrations. By screening the chemical library of the Screening Committee of Anticancer Drugs, we identified the histone deacetylase (HDAC) inhibitor romidepsin (FK228) and its novel analogs. In vitro PI3K activity assays confirmed that these compounds directly inhibit PI3K activity at μM‐range concentrations. FK‐A5 analog was the most potent inhibitor. Western blotting revealed that these compounds inhibit phosphorylation of protein kinase B and downstream signaling components. Molecular modeling of the PI3K–FK228 complex indicated that FK228 binds to the ATP‐binding pocket of PI3K. At μM‐range concentrations, FK228 and FK‐A5 show potent cytotoxicity, inducing apoptosis even in HDAC inhibitor‐resistant cells. Furthermore, HDAC/PI3K dual inhibition by FK228 and FK‐A5 at μM‐range concentrations potentiates the apoptosis induction, mimicking the effect of combining specific HDAC and PI3K inhibitors. In this study, we showed that FK228 and its analogs directly inhibit PI3K activity and induce apoptosis at μM‐range concentrations, similar to HDAC/PI3K dual inhibition. In future, optimizing the potency of FK228 and its analogs against PI3K may contribute to the development of novel HDAC/PI3K dual inhibitors for cancer treatment.
Semaphorin 3C is involved in the progression of gastric cancer
Authors: Miyato Hideyo , Tsuno Nelson Hirokazu , Kitayama Joji
Published: August 2012

Malignant tumors are often associated with denervation, suggesting the functional implication of axonal guidance molecules in tumor growth. Here, we assessed the role of semaphorin 3C (sema3C) in the progression of gastric cancer. Immunohistochemistry of human samples revealed that sema3C was strongly expressed in neoplastic cells, especially at the invasion front. Stable transfection of target sequences of sema3C miRNA did not affect the in vitro proliferative activity of human gastric cancer AZ‐521 cells. However, when the tumor growth was examined in vivo using an orthotopic model in nude mice, primary stomach tumors as well as metastatic liver tumors were significantly suppressed by sema3C silencing with the reduction of microvessel density. Immunostaining of primary tumor indicated the rate of Ki‐67 positive carcinoma cells was decreased, whereas that of apoptotic cells was significantly increased in sema3C‐silenced tumor. In addition, capillary‐like tubular formation was reduced by the addition of culture media of sema3C miRNA cells compared with the media of control miRNA cells. Semaphorin 3C is positively expressed in gastric cancer cells and may be involved in tumor progression, presumably through the stimulation of angiogenesis.