bluuebunny/crossref_metadata_2025 huggingface dataset:
Driven Brownian coagulation of polymers
Authors: Krapivsky P. L. , Connaughton Colm
Published: May 2012

We present an analysis of the mean-field kinetics of Brownian coagulation of droplets and polymers driven by input of monomers which aims to characterize the long time behavior of the cluster size distribution as a function of the inverse fractal dimension, a, of the aggregates. We find that two types of long time behavior are possible. For $0\le a < \frac{1}{2}$0≤a<12 the size distribution reaches a stationary state with a power law distribution of cluster sizes having exponent $\frac{3}{2}$32. The amplitude of this stationary state is determined exactly as a function of a. For $\frac{1}{2} < a \le 1$12<a≤1, the cluster size distribution never reaches a stationary state. Instead a bimodal distribution is formed in which a narrow population of small clusters near the monomer scale is separated by a gap (where the cluster size distribution is effectively zero) from a population of large clusters which continue to grow for all time by absorbing small clusters. The marginal case, $a=\frac{1}{2}$a=12, is difficult to analyze definitively, but we argue that the cluster size distribution becomes stationary and there is a logarithmic correction to the algebraic tail.
Zinc oxide micro-spheres with faceted surfaces produced by laser ablation of zinc targets
Authors: Chen Ming , Liu Xiangdong , Liu Yuehua , Zhao Mingwen
Published: May 2012

We report the fabrication of ZnO micro-spheres using high-power laser ablation of Zn metal in the presence of oxygen gas background without use of any catalysts or additives. The centre-symmetric geometrical structures of ZnO micro-spheres exhibit clear pentagonal and hexagonal facets with different sizes. A discussion of the growth mechanisms based on a model of subsurface micro-explosion boiling followed by laser-surface sintering of assembled particles has been proposed to explain the formation of the ZnO micro-spheres.
Study of photoexcitations in poly(3-hexylthiophene) for photovoltaic applications
Authors: Hukic-Markosian Golda , Basel Tek , Singh Sanjeev , Valy Vardeny Z. , Li Sergey , Laird Darin
Published: May 2012

We used a variety of steady state and transient optical techniques for studying the primary and steady state photoexcitations in pristine films of poly(3-hexylthiophene) [P3HT] with different molecular weight used for organic photovoltaic solar cells. The employed techniques include picosecond transient and steady state photoluminescence and photomodulation spectroscopies, laser action, and doping induced absorption. We show that solar cell device qualities based on donor-acceptor blends of the P3HT polymers with substituted fullerene molecules crucially depend on the polymer properties, which can be readily discerned by the steady state photomodulation technique. This technique can, therefore, be applied to specific polymer donors for estimating their solar cell device properties prior to actually fabricating an optimal device.
Angular and energy distribution of fragment ions in dissociative double photoionization of acetylene molecules at 39 eV
Authors: Alagia M. , Callegari C. , Candori P. , Falcinelli S. , Pirani F. , Richter R. , Stranges S. , Vecchiocattivi F.
Published: May 2012

The two-body dissociation reactions of the dication, ${\rm C}_{\rm 2} {\rm H}_{\rm 2}^{{\rm 2 + }}$C2H22+, produced by 39.0 eV double photoionization of acetylene molecules, have been studied by coupling photoelectron-photoion-photoion coincidence and ion imaging techniques. The results provide the kinetic energy and angular distributions of product ions. The analysis of the results indicates that the dissociation leading to C2H++H+ products occurs through a metastable dication with a lifetime of 108 ± 22 ns, and a kinetic energy release (KER) distribution exhibiting a maximum at ∼4.3 eV with a full width at half maximum (FWHM) of about 60%. The reaction leading to ${\rm CH}_{\rm 2}^{\rm + } + {\rm C}^{\rm + }$ CH 2++C+ occurs in a time shorter than the typical rotational period of the acetylene molecules (of the order of 10−12 s). The KER distribution of product ions for this reaction, exhibits a maximum at ∼4.5 eV with a FWHM of about 28%. The symmetric dissociation, leading to CH+ + CH+, exhibits a KER distribution with a maximum at ∼5.2 eV with a FWHM of 44%. For the first two reactions the angular distributions of ion products also indicate that the double photoionization of acetylene occurs when the neutral molecule is mainly oriented perpendicularly to the light polarization vector.
Time resolved pump-probe scattering in MnAs/GaAs(001): A look into the dynamics of α-β stripe domains
Authors: Sacchi Maurizio , Spezzani Carlo , Allaria Enrico , Ferrari Eugenio , Coreno Marcello , Marangolo Massimiliano , Eddrief Mahmoud , Etgens Victor , De Ninno Giovanni
Published: May 2012

Scattering of 130 nm radiation with 100 fs pulse length was used to monitor the α/β-striped microstructure in MnAs/GaAs(001), after a 390 nm 5 mJcm−2 pump pulse. A strong reduction of the Bragg peak intensity, corresponding to a widening of the β-stripes, takes place with a characteristic time of 15 ps. These results are relevant within the context of using MnAs/GaAs(001) as a template for the growth of ferromagnetic films, whose magnetization direction can be controlled by modifying the template temperature.
Spin-charge-orbital coupling in multiferroic LuFe2O4 thin films
Authors: Rai R. C. , Delmont A. , Sprow A. , Cai B. , Nakarmi M. L.
Published: May 2012

We report optical, electronic, and electrical properties of LuFe2O4 thin films deposited on (001) sapphire and (111) YSZ substrates by electron beam deposition. The absorption spectra of LuFe2O4 thin films contain several electronic transitions above its direct energy band gap of ∼2.18 eV at 300 K. The Fe2+ d to d on-site and O 2p to Fe 3d charge-transfer electronic transitions display a ferrimagnetic transition at ∼235 ± 5 K and the charge-ordered transition at ∼350 ± 10 K. Resistivity and the energy band gap also exhibit the two transitions, confirming a strong spin-charge-orbital coupling in the LuFe2O4 thin film.
Interfacial confinement in core-shell nanowires due to high dielectric mismatch
Authors: Sousa A. A. , Pereira T. A. S. , Chaves A. , de Sousa J. S. , Farias G. A.
Published: May 2012

We theoretically investigate the role of the dielectric mismatch between materials on the energy levels and recombination energies of a core-shell nanowire. Our results demonstrate that when the dielectric constant of the core material is lower than that of the shell material, the self-image potential pushes the charge carriers towards the core-shell interface in such a way that the ideal confinement model is no longer suitable. The effects of this interfacial confinement on the electronic properties of such wires, as well as on its response to applied magnetic fields, are discussed.
Silicon nanowire atomic force microscopy probes for high aspect ratio geometries
Authors: Bryce Brian A. , Robert Ilic B. , Reuter Mark C. , Tiwari Sandip
Published: May 2012

Using site controlled growth of single vapor-liquid-solid silicon nanowires high aspect ratio atomic force microscope probes are fabricated on a wafer scale. Nanowire probe aspect ratios as high as 90:1 are demonstrated. Probe performance and limitations are explored by imaging high aspect ratio etched silicon structures using atomic force microscopy. Silicon nanowire probes are an ideal platform for non-destructive topographic imaging of high aspect ratio features.
Acceptor-like deep level defects in ion-implanted ZnO
Authors: Vines L. , Wong-Leung J. , Jagadish C. , Quemener V. , Monakhov E. V. , Svensson B. G.
Published: May 2012

N-type ZnO samples have been implanted with MeV Zn+ ions at room temperature to doses between 1×108 and 2×1010cm-2, and the defect evolution has been studied by capacitance-voltage and deep level transient spectroscopy measurements. The results show a dose dependent compensation by acceptor-like defects along the implantation depth profile, and at least four ion-induced deep-level defects arise, where two levels with energy positions of 1.06 and 1.2 eV below the conduction band increase linearly with ion dose and are attributed to intrinsic defects. Moreover, a re-distribution of defects as a function of depth is observed already at temperatures below 400 K.
Note: Long range and accurate measurement of deep trench microstructures by a specialized scanning tunneling microscope
Authors: Ju Bing-Feng , Chen Yuan-Liu , Zhang Wei , Zhu Wule , Jin Chao , Fang F. Z.
Published: May 2012

A compact but practical scanning tunneling microscope (STM) with high aspect ratio and high depth capability has been specially developed. Long range scanning mechanism with tilt-adjustment stage is adopted for the purpose of adjusting the probe-sample relative angle to compensate the non-parallel effects. A periodical trench microstructure with a pitch of 10 μm has been successfully imaged with a long scanning range up to 2.0 mm. More innovatively, a deep trench with depth and step height of 23.0 μm has also been successfully measured, and slope angle of the sidewall can approximately achieve 67°. The probe can continuously climb the high step and exploring the trench bottom without tip crashing. The new STM could perform long range measurement for the deep trench and high step surfaces without image distortion. It enables accurate measurement and quality control of periodical trench microstructures.
Terahertz time-domain spectroscopy of anisotropic complex conductivity tensors in silicon nanowire films
Authors: Lim Meehyun , Choi Sung-Jin , Lee Gyu-Seok , Seol Myeong-Lok , Do Youngwoong , Choi Yang-Kyu , Han Haewook
Published: May 2012

The effective complex conductivity tensor of a highly anisotropic, vertically aligned silicon nanowire film was measured by terahertz time-domain spectroscopy. The silicon nanowires were fabricated on a p-type silicon substrate by metal-assisted chemical etching, which resulted in a film with uniaxially anisotropic optical properties. The measured terahertz transverse and longitudinal conductivity values were in excellent agreement with the results of calculations based on the Drude-Smith and Lorentz models, respectively.
Image acceleration in parallel magnetic resonance imaging by means of metamaterial magnetoinductive lenses
Authors: Freire Manuel J. , Lopez Marcos A. , Algarin Jose M. , Breuer Felix , Marqués Ricardo
Published: May 2012

Parallel Magnetic Resonance imaging (pMRI) is an image acceleration technique which takes advantage of localized sensitivities of multiple receivers. In this letter, we show that metamaterial lenses based on capacitively-loaded rings can provide higher localization of coil sensitivities compared to conventional loop designs. Several lens designs are systematically analyzed in order to find the structure providing higher signal-to-noise-ratio. The magnetoinductive (MI) lens has been found to be the optimum structure and an experiment is developed to show it. The ability of the MI lens for pMRI is investigated by means of the parameter known in the MRI community as g-Factor.
Release of dendritic cells from cognate CD4+T-cell recognition results in impaired peripheral tolerance and fatal cytotoxic T-cell mediated autoimmunity
Authors: Muth Sabine , Schütze Kristian , Schild Hansjörg , Probst Hans Christian
Published: May 2012

Resting dendritic cells (DCs) induce tolerance of peripheral T cells that have escaped thymic negative selection and thus contribute significantly to protection against autoimmunity. We recently showed that CD4+Foxp3+regulatory T cells (Tregs) are important for maintaining the steady-state phenotype of DCs and their tolerizing capacity in vivo. We now provide evidence that DC activation in the absence of Tregs is a direct consequence of missing DC–Treg interactions rather than being secondary to generalized autoimmunity in Treg-less mice. We show that DCs that lack MHC class II and thus cannot make cognate interactions with CD4+T cells are completely unable to induce peripheral CD8+T-cell tolerance. Consequently, mice in which interactions between DC and CD4+T cells are not possible develop spontaneous and fatal cytotoxic T lymphocyte-mediated autoimmunity.
Oncogene-mediated alterations in chromatin conformation
Authors: Rickman David S. , Soong T. David , Moss Benjamin , Mosquera Juan Miguel , Dlabal Jan , Terry Stéphane , MacDonald Theresa Y. , Tripodi Joseph , Bunting Karen , Najfeld Vesna , Demichelis Francesca , Melnick Ari M. , Elemento Olivier , Rubin Mark A.
Published: May 2012

Emerging evidence suggests that chromatin adopts a nonrandom 3D topology and that the organization of genes into structural hubs and domains affects their transcriptional status. How chromatin conformation changes in diseases such as cancer is poorly understood. Moreover, how oncogenic transcription factors, which bind to thousands of sites across the genome, influence gene regulation by globally altering the topology of chromatin requires further investigation. To address these questions, we performed unbiased high-resolution mapping of intra- and interchromosome interactions upon overexpression of ERG, an oncogenic transcription factor frequently overexpressed in prostate cancer as a result of a gene fusion. By integrating data from genome-wide chromosome conformation capture (Hi-C), ERG binding, and gene expression, we demonstrate that oncogenic transcription factor overexpression is associated with global, reproducible, and functionally coherent changes in chromatin organization. The results presented here have broader implications, as genomic alterations in other cancer types frequently give rise to aberrant transcription factor expression, e.g., EWS-FLI1, c-Myc, n-Myc, and PML-RARα.
Contributions of cultural services to the ecosystem services agenda
Authors: Daniel Terry C. , Muhar Andreas , Arnberger Arne , Aznar Olivier , Boyd James W. , Chan Kai M. A. , Costanza Robert , Elmqvist Thomas , Flint Courtney G. , Gobster Paul H. , Grêt-Regamey Adrienne , Lave Rebecca , Muhar Susanne , Penker Marianne , Ribe Robert G. , Schauppenlehner Thomas , Sikor Thomas , Soloviy Ihor , Spierenburg Marja , Taczanowska Karolina , Tam Jordan , von der Dunk Andreas
Published: May 2012

Cultural ecosystem services (ES) are consistently recognized but not yet adequately defined or integrated within the ES framework. A substantial body of models, methods, and data relevant to cultural services has been developed within the social and behavioral sciences before and outside of the ES approach. A selective review of work in landscape aesthetics, cultural heritage, outdoor recreation, and spiritual significance demonstrates opportunities for operationally defining cultural services in terms of socioecological models, consistent with the larger set of ES. Such models explicitly link ecological structures and functions with cultural values and benefits, facilitating communication between scientists and stakeholders and enabling economic, multicriterion, deliberative evaluation and other methods that can clarify tradeoffs and synergies involving cultural ES. Based on this approach, a common representation is offered that frames cultural services, along with all ES, by the relative contribution of relevant ecological structures and functions and by applicable social evaluation approaches. This perspective provides a foundation for merging ecological and social science epistemologies to define and integrate cultural services better within the broader ES framework.
Evolutionary optimum for male sexual traits characterized using the multivariate Robertson–Price Identity
Authors: Delcourt Matthieu , Blows Mark W. , Aguirre J. David , Rundle Howard D.
Published: May 2012

Phenotypes tend to remain relatively constant in natural populations, suggesting a limit to trait evolution. Although stationary phenotypes suggest stabilizing selection, directional selection is more commonly reported. However, selection on phenotypes will have no evolutionary consequence if the traits do not genetically covary with fitness, a covariance known as the Robertson–Price Identity. The nature of this genetic covariance determines if phenotypes will evolve directionally or whether they reside at an evolutionary optimum. Here, we show how a set of traits can be shown to be under net stabilizing selection through an application of the multivariate Robertson–Price Identity. We characterize how a suite of male sexual displays genetically covaries with fitness in a population of
Drosophila serrata
. Despite strong directional sexual selection on these phenotypes directly and significant genetic variance in them, little genetic covariance was detected with overall fitness. Instead, genetic analysis of trait deviations showed substantial stabilizing selection on the genetic variance of these traits with respect to overall fitness, indicating that they reside at an evolutionary optimum. In the presence of widespread pleiotropy, stabilizing selection on focal traits will arise through the net effects of selection on other, often unmeasured, traits and will tend to be stronger on trait combinations than single traits. Such selection may be difficult to detect in phenotypic analyses if the environmental covariance between the traits and fitness obscures the underlying genetic associations. The genetic analysis of trait deviations provides a way of detecting the missing stabilizing selection inferred by recent metaanalyses.
Predominance of heavily calcified coccolithophores at low CaCO
3
saturation during winter in the Bay of Biscay
Authors: Smith Helen E. K. , Tyrrell Toby , Charalampopoulou Anastasia , Dumousseaud Cynthia , Legge Oliver J. , Birchenough Sarah , Pettit Laura R. , Garley Rebecca , Hartman Sue E. , Hartman Mark C. , Sagoo Navjit , Daniels Chris J. , Achterberg Eric P. , Hydes David J.
Published: May 2012

Coccolithophores are an important component of the Earth system, and, as calcifiers, their possible susceptibility to ocean acidification is of major concern. Laboratory studies at enhanced
p
CO
2
levels have produced divergent results without overall consensus. However, it has been predicted from these studies that, although calcification may not be depressed in all species, acidification will produce “a transition in dominance from more to less heavily calcified coccolithophores” [Ridgwell A, et al., (2009)
Biogeosciences
6:2611–2623]. A recent observational study [Beaufort L, et al., (2011)
Nature
476:80–83] also suggested that coccolithophores are less calcified in more acidic conditions. We present the results of a large observational study of coccolithophore morphology in the Bay of Biscay. Samples were collected once a month for over a year, along a 1,000-km-long transect. Our data clearly show that there is a pronounced seasonality in the morphotypes of
Emiliania huxleyi
, the most abundant coccolithophore species. Whereas pH and CaCO
3
saturation are lowest in winter, the
E. huxleyi
population shifts from <10% (summer) to >90% (winter) of the heavily calcified form. However, it is unlikely that the shifts in carbonate chemistry alone caused the morphotype shift. Our finding that the most heavily calcified morphotype dominates when conditions are most acidic is contrary to the earlier predictions and raises further questions about the fate of coccolithophores in a high-CO
2
world.
Cellular mechanical properties reflect the differentiation potential of adipose-derived mesenchymal stem cells
Authors: González-Cruz Rafael D. , Fonseca Vera C. , Darling Eric M.
Published: May 2012

The mechanical properties of adipose-derived stem cell (ASC) clones correlate with their ability to produce tissue-specific metabolites, a finding that has dramatic implications for cell-based regenerative therapies. Autologous ASCs are an attractive cell source due to their immunogenicity and multipotent characteristics. However, for practical applications ASCs must first be purified from other cell types, a critical step which has proven difficult using surface-marker approaches. Alternative enrichment strategies identifying broad categories of tissue-specific cells are necessary for translational applications. One possibility developed in our lab uses single-cell mechanical properties as predictive biomarkers of ASC clonal differentiation capability. Elastic and viscoelastic properties of undifferentiated ASCs were tested via atomic force microscopy and correlated with lineage-specific metabolite production. Cell sorting simulations based on these “mechanical biomarkers” indicated they were predictive of differentiation capability and could be used to enrich for tissue-specific cells, which if implemented could dramatically improve the quality of regenerated tissues.
Parasite diversity and coinfection determine pathogen infection success and host fitness
Authors: Johnson Pieter T. J. , Hoverman Jason T.
Published: May 2012

While the importance of changes in host biodiversity for disease risk continues to gain empirical support, the influence of natural variation in parasite diversity on epidemiological outcomes remains largely overlooked. Here, we combined field infection data from 2,191 amphibian hosts representing 158 parasite assemblages with mechanistic experiments to evaluate the influence of parasite richness on both parasite transmission and host fitness. Using a guild of larval trematode parasites (six species) and an amphibian host, our experiments contrasted the effects of parasite richness vs. composition, observed vs. randomized assemblages, and additive vs. replacement designs. Consistent with the dilution effect hypothesis extended to intrahost diversity, increases in parasite richness reduced overall infection success, including infections by the most virulent parasite. However, the effects of parasite richness on host growth and survival were context dependent; pathology increased when parasites were administered additively, even when the presence of the most pathogenic species was held constant, but decreased when added species replaced or reduced virulent species, emphasizing the importance of community composition and assembly. These results were similar or stronger when community structures were weighted by their observed frequencies in nature. The field data also revealed the highly nested structure of parasite assemblages, with virulent species generally occupying basal positions, suggesting that increases in parasite richness and antagonism in nature will decrease virulent infections. Our findings emphasize the importance of parasite biodiversity and coinfection in affecting epidemiological responses and highlight the value of integrating research on biodiversity and community ecology for understanding infectious diseases.
Rewritable digital data storage in live cells via engineered control of recombination directionality
Authors: Bonnet Jerome , Subsoontorn Pakpoom , Endy Drew
Published: May 2012

The use of synthetic biological systems in research, healthcare, and manufacturing often requires autonomous history-dependent behavior and therefore some form of engineered biological memory. For example, the study or reprogramming of aging, cancer, or development would benefit from genetically encoded counters capable of recording up to several hundred cell division or differentiation events. Although genetic material itself provides a natural data storage medium, tools that allow researchers to reliably and reversibly write information to DNA in vivo are lacking. Here, we demonstrate a rewriteable recombinase addressable data (RAD) module that reliably stores digital information within a chromosome. RAD modules use serine integrase and excisionase functions adapted from bacteriophage to invert and restore specific DNA sequences. Our core RAD memory element is capable of passive information storage in the absence of heterologous gene expression for over 100 cell divisions and can be switched repeatedly without performance degradation, as is required to support combinatorial data storage. We also demonstrate how programmed stochasticity in RAD system performance arising from bidirectional recombination can be achieved and tuned by varying the synthesis and degradation rates of recombinase proteins. The serine recombinase functions used here do not require cell-specific cofactors and should be useful in extending computing and control methods to the study and engineering of many biological systems.
Rethinking dog domestication by integrating genetics, archeology, and biogeography
Authors: Larson Greger , Karlsson Elinor K. , Perri Angela , Webster Matthew T. , Ho Simon Y. W. , Peters Joris , Stahl Peter W. , Piper Philip J. , Lingaas Frode , Fredholm Merete , Comstock Kenine E. , Modiano Jaime F. , Schelling Claude , Agoulnik Alexander I. , Leegwater Peter A. , Dobney Keith , Vigne Jean-Denis , Vilà Carles , Andersson Leif , Lindblad-Toh Kerstin
Published: May 2012

The dog was the first domesticated animal but it remains uncertain when the domestication process began and whether it occurred just once or multiple times across the Northern Hemisphere. To ascertain the value of modern genetic data to elucidate the origins of dog domestication, we analyzed 49,024 autosomal SNPs in 1,375 dogs (representing 35 breeds) and 19 wolves. After combining our data with previously published data, we contrasted the genetic signatures of 121 breeds with a worldwide archeological assessment of the earliest dog remains. Correlating the earliest archeological dogs with the geographic locations of 14 so-called “ancient” breeds (defined by their genetic differentiation) resulted in a counterintuitive pattern. First, none of the ancient breeds derive from regions where the oldest archeological remains have been found. Second, three of the ancient breeds (Basenjis, Dingoes, and New Guinea Singing Dogs) come from regions outside the natural range of
Canis lupus
(the dog’s wild ancestor) and where dogs were introduced more than 10,000 y after domestication. These results demonstrate that the unifying characteristic among all genetically distinct so-called ancient breeds is a lack of recent admixture with other breeds likely facilitated by geographic and cultural isolation. Furthermore, these genetically distinct ancient breeds only appear so because of their relative isolation, suggesting that studies of modern breeds have yet to shed light on dog origins. We conclude by assessing the limitations of past studies and how next-generation sequencing of modern and ancient individuals may unravel the history of dog domestication.
Pulse-induced nonequilibrium dynamics of acetylene inside carbon nanotube studied by an ab initio approach
Authors: Miyamoto Yoshiyuki , Zhang Hong , Rubio Angel
Published: May 2012

Nanoscale molecular confinement substantially modifies the functionality and electronic properties of encapsulated molecules. Many works have approached this problem from the perspective of quantifying ground-state molecular changes, but little is known about the nonequilibrium dynamics of encapsulated molecular system. In this letter, we report an analysis of the nonequilibrium dynamics of acetylene (C
2
H
2
) inside a semiconducting carbon nanotube (CNT). An ultrashort high-intense laser pulse (2 fs width and 10
15
 W/cm
2
intensity) brings the systems out of equilibrium. This process is modeled by comprehensive first-principles time-dependent density-functional simulations. When encapsulated, acetylene dimer, unlike a single acetylene molecule, exhibits correlated vibrational dynamics (C–C bond rotation and H–C–C bending) that is markedly different from the dynamics observed in the gas phase. This result highlights the role of CNT in modulating the optical electric field within the tube. At longer simulation timescales (> 20 fs) in the largest-diameter tube studied here [CNT(14,0)], we observe synchronized rotation about the C–C axes in the dimer and ultimately ejection of one of the four hydrogen atoms. Our results illustrate the richness of photochemical phenomena in confined geometries.
Model for
MLL
translocations in therapy-related leukemia involving topoisomerase IIβ-mediated DNA strand breaks and gene proximity
Authors: Cowell Ian G. , Sondka Zbyslaw , Smith Kayleigh , Lee Ka Cheong , Manville Catriona M. , Sidorczuk-Lesthuruge Malgorzata , Rance Holly Ashlene , Padget Kay , Jackson Graham Hunter , Adachi Noritaka , Austin Caroline A.
Published: May 2012

Topoisomerase poisons such as the epipodophyllotoxin etoposide are widely used effective cytotoxic anticancer agents. However, they are associated with the development of therapy-related acute myeloid leukemias (t-AMLs), which display characteristic balanced chromosome translocations, most often involving the mixed lineage leukemia (
MLL
) locus at 11q23.
MLL
translocation breakpoints in t-AMLs cluster in a DNase I hypersensitive region, which possesses cryptic promoter activity, implicating transcription as well as topoisomerase II activity in the translocation mechanism. We find that 2–3% of
MLL
alleles undergoing transcription do so in close proximity to one of its recurrent translocation partner genes,
AF9
or
AF4
, consistent with their sharing transcription factories. We show that most etoposide-induced chromosome breaks in the
MLL
locus and the overall genotoxicity of etoposide are dependent on topoisomerase IIβ, but that topoisomerase IIα and -β occupancy and etoposide-induced DNA cleavage data suggest factors other than local topoisomerase II concentration determine specific clustering of
MLL
translocation breakpoints in t-AML. We propose a model where DNA double-strand breaks (DSBs) introduced by topoisomerase IIβ into pairs of genes undergoing transcription within a common transcription factory become stabilized by antitopoisomerase II drugs such as etoposide, providing the opportunity for illegitimate end joining and translocation.
Primate evidence on the late health effects of early-life adversity
Authors: Conti Gabriella , Hansman Christopher , Heckman James J. , Novak Matthew F. X. , Ruggiero Angela , Suomi Stephen J.
Published: May 2012

This paper exploits a unique ongoing experiment to analyze the effects of early rearing conditions on physical and mental health in a sample of rhesus monkeys (
Macaca mulatta
). We analyze the health records of 231 monkeys that were randomly allocated at birth across three rearing conditions: mother rearing, peer rearing, and surrogate peer rearing. We show that the lack of a secure attachment relationship in the early years engendered by adverse rearing conditions has detrimental long-term effects on health that are not compensated for by a normal social environment later in life.
Intracerebral chondroitinase ABC and heparan sulfate proteoglycan glypican improve outcome from chronic stroke in rats
Authors: Hill Justin J. , Jin Kunlin , Mao Xiao Ou , Xie Lin , Greenberg David A.
Published: May 2012

Physical and chemical constraints imposed by the periinfarct glial scar may contribute to the limited clinical improvement often observed after ischemic brain injury. To investigate the role of some of these mediators in outcome from cerebral ischemia, we treated rats with the growth-inhibitory chondroitin sulfate proteoglycan neurocan, the growth-stimulating heparan sulfate proteoglycan glypican, or the chondroitin sulfate proteoglycan-degrading enzyme chondroitinase ABC. Neurocan, glypican, or chondroitinase ABC was infused directly into the infarct cavity for 7 d, beginning 7 d after middle cerebral artery occlusion. Glypican and chondroitinase ABC reduced glial fibrillary acidic protein immunoreactivity and increased microtubule-associated protein-2 immunoreactivity in the periinfarct region, and glypican- and chondroitinase ABC-treated rats showed behavioral improvement compared with neurocan- or saline-treated rats. Glypican and chondroitinase ABC also increased neurite extension in cortical neuron cultures. Glypican increased fibroblast growth factor-2 expression and chondroitinase ABC increased brain-derived neurotrophic factor expression in these cultures, whereas no such effects were seen following neurocan treatment. Thus, treatment with glypican or enzymatic disruption of neurocan with chondroitinase ABC improves gross anatomical, histological, and functional outcome in the chronic phase of experimental stroke in rats. Changes in growth factor expression and neuritogenesis may help to mediate these effects.
Surgical removal of the parametrial fat pads stimulates apoptosis and inhibits UVB-induced carcinogenesis in mice fed a high-fat diet
Authors: Lu Yao-Ping , Lou You-Rong , Bernard Jamie J. , Peng Qing-Yun , Li Tao , Lin Yong , Shih Weichung Joe , Nghiem Paul , Shapses Sue , Wagner George C. , Conney Allan H.
Published: May 2012

Removal of the parametrial fat pads (partial lipectomy) from female SKH-1 mice fed a high-fat diet inhibited UVB-induced carcinogenesis, but this was not observed in mice fed a low-fat chow diet. Partial lipectomy in high-fat–fed mice decreased the number of keratoacanthomas and squamous cell carcinomas per mouse by 76 and 79%, respectively, compared with sham-operated control mice irradiated with UVB for 33 wk. Immunohistochemical analysis indicated that partial lipectomy increased caspase 3 (active form) positive cells by 48% in precancerous epidermis away from tumors, by 68% in keratoacanthomas, and by 224% in squamous cell carcinomas compared with sham-operated control mice. In addition, partial lipectomy decreased cell proliferation away from tumors and in tumors. RT-PCR analysis for adipokines revealed that mRNAs for TIMP1, MCP1, and SerpinE1 (proinflammatory/antiapoptotic cytokines) in the parametrial fat pads of sham-operated control mice were 54- to 83-fold higher than levels in compensatory fat that returned after surgery in partially lipectomized mice at the end of the tumor study. Feeding mice high-fat diets for 2 wk increased levels of TIMP1 and other adipokines in serum and epidermis, and these increases were inhibited by removal of the parametrial fat pads. Our results are a unique demonstration that surgical removal of a specific tissue fat results in inhibition of carcinogenesis in obese mice. This inhibition was associated with an increase in apoptosis and a decrease in proliferation in tumors and in precancerous areas away from tumors.
Iterated Prisoner’s Dilemma contains strategies that dominate any evolutionary opponent
Authors: Press William H. , Dyson Freeman J.
Published: May 2012

The two-player Iterated Prisoner’s Dilemma game is a model for both sentient and evolutionary behaviors, especially including the emergence of cooperation. It is generally assumed that there exists no simple ultimatum strategy whereby one player can enforce a unilateral claim to an unfair share of rewards. Here, we show that such strategies unexpectedly do exist. In particular, a player X who is witting of these strategies can (
i
) deterministically set her opponent Y’s score, independently of his strategy or response, or (
ii
) enforce an extortionate linear relation between her and his scores. Against such a player, an evolutionary player’s best response is to accede to the extortion. Only a player with a theory of mind about his opponent can do better, in which case Iterated Prisoner’s Dilemma is an Ultimatum Game.
Structural differences between apoE3 and apoE4 may be useful in developing therapeutic agents for Alzheimer’s disease
Authors: Frieden Carl , Garai Kanchan
Published: May 2012

Apolipoproteins E3 and E4, proteins with a molecular mass of 34.15 kDa, differ by a single amino acid change. ApoE4 contains an arginine residue at position 112, whereas apoE3 has a cysteine at this position. ApoE4 is the major risk factor for late-onset Alzheimer’s disease, whereas apoE3, the common isoform, is neutral with respect to this disease. Here, using literature data from both hydrogen-deuterium exchange and site-directed mutations, we suggest structural differences between these two isoforms that are distant from the site of the arginine-to-cysteine change. These structural differences involve sequences from both the N- and C-terminal domains, sequentially far apart but structurally close. In addition, these regions are close to regions that bind lipid and to a region involved in association of apoE monomers to higher molecular weight forms. We discuss the possibility that these regions could be targeted preferentially to affect the function of apoE4 relative to apoE3.
A Study of the Spawning Ecology and Early Life History Survival of Bonneville Cutthroat Trout
Authors: Budy Phaedra , Wood Sara , Roper Brett
Published: May 2012

We completed a large-scale field experiment in four tributaries of the Logan River, Utah, where the largest metapopulation of imperiled Bonneville cutthroat trout Oncorhynchus clarkii utah persists. We documented the spatial and temporal distributions of spawners, quantified substrate use versus substrate availability, and evaluated differences in hatch and emergence fry success between and among sites in relation to habitat characteristics. We observed considerable variability in the timing, magnitude, and duration of spawning among study areas (streams), in part as a function of a variable, multipeaked hydrograph. Nevertheless, across study areas, >70% of redds were constructed on the final descending limb of the hydrograph. Despite large differences in the amount of spawning substrate available, Bonneville cutthroat trout utilized a narrow range of substrate and sizes (3–80 mm) similar to that utilized by other subspecies of cutthroat trout, albeit biased towards larger sizes. Water temperatures generally remained below the recommended range (6–17°C) for spawning; however, the viability of this metapopulation of cutthroat trout suggests that the recommended temperature range for spawning is overestimated for this subspecies and (or) does not account for local thermal adaptation. Hatch varied from 43% to 77% and emergence survival from 39% to 65% among streams, and within-stream variability was substantial; both survival rates declined significantly as a function of increased fine sediment concentrations. Egg development rates were nearly 50% greater in a high-elevation tributary where redd counts were also lowest. In high, mountain systems with short growing seasons, this incubation delay likely presents a significant growth disadvantage for age-0 trout. Our research enhances our understanding of Bonneville cutthroat trout spawning ecology and early survival and provides critical information for aiding in the development of benchmarks for their recovery. Effective conservation efforts should be directed towards minimizing anthropogenic activities that result in excess sedimentation in their critical spawning tributaries.

Received April 15, 2011; accepted February 7, 2012
An Expert Panel Approach to Assessing Potential Effects of Bull Trout Reintroduction on Federally Listed Salmonids in the Clackamas River, Oregon
Authors: Marcot Bruce G. , Allen Chris S. , Morey Steve , Shively Dan , White Rollie
Published: May 2012

The bull trout Salvelinus confluentus is an apex predator in native fish communities in the western USA and is listed as threatened under the U.S. Endangered Species Act (ESA). Restoration of this species has raised concerns over its potential predatory impacts on native fish fauna. We held a five-person expert panel to help determine potential impacts of reintroducing bull trout into the Clackamas River, northwest Oregon, on the viability of four anadromous salmonid populations that are listed as threatened under the ESA: spring and fall Chinook salmon Oncorhynchus tshawytscha, coho salmon O. kisutch, and winter steelhead O. mykiss. The panel session was rigorously structured and used a modified Delphi process with structured expert elicitation, disclosure, discussion, and brainstorming. Each panelist distributed 100 score points among seven categories of potential bull trout impact (from no impact to very high impact) on extinction probabilities for the anadromous salmonids. Results were provided by individual panelists rather than as a group consensus and were summarized as means and variations in scores to express the panelists’ individual uncertainty, variability among the panelists, and expected differences among the affected salmonids. Score results suggested that panelists viewed the potential impact of bull trout as very low or moderately low for spring Chinook salmon, coho salmon, and winter steelhead and mostly none to very low for fall Chinook salmon. Panelists also provided 19 possible monitoring activities and 21 possible management actions for assessing potential impacts and taking remedial action if bull trout are found to have unacceptable adverse effects. Results of the panel were used by the U.S. Fish and Wildlife Service to help craft and execute a plan to reintroduce bull trout into the Clackamas River system under the ESA. This rigorous expert panel process can be used for a wide range of evaluations in situations where empirical data are sparse or ecological interactions are too complex for explicit analytic solution.

Received September 5, 2011; revised December 12, 2011; accepted January 3, 2012
TBC1D14 regulates autophagosome formation via Rab11- and ULK1-positive recycling endosomes
Authors: Longatti Andrea , Lamb Christopher A. , Razi Minoo , Yoshimura Shin-ichiro , Barr Francis A. , Tooze Sharon A.
Published: May 2012

Autophagy is a bulk degradation process characterized by the formation of double membrane vesicles called autophagosomes. The exact molecular mechanism of autophagosome formation and the origin of the autophagosomal membrane remain unclear. We screened 38 human Tre-2/Bub2/Cdc16 domain–containing Rab guanosine triphosphatase–activating proteins (GAPs) and identified 11 negative regulators of starvation-induced autophagy. One of these putative RabGAPs, TBC1D14, colocalizes and interacts with the autophagy kinase ULK1. Overexpressed TBC1D14 tubulates ULK1-positive recycling endosomes (REs), impairing their function and inhibiting autophagosome formation. TBC1D14 binds activated Rab11 but is not a GAP for Rab11, and loss of Rab11 prevents TBC1D14-induced tubulation of REs. Furthermore, Rab11 is required for autophagosome formation. ULK1 and Atg9 are found on Rab11- and transferrin (Tfn) receptor (TfnR)–positive recycling endosomes. Amino acid starvation causes TBC1D14 to relocalize from REs to the Golgi complex, whereas TfnR and Tfn localize to forming autophagosomes, which are ULK1 and LC3 positive. Thus, TBC1D14- and Rab11-dependent vesicular transport from REs contributes to and regulates starvation-induced autophagy.
Pericytes support neutrophil subendothelial cell crawling and breaching of venular walls in vivo
Authors: Proebstl Doris , Voisin Mathieu-Benoît , Woodfin Abigail , Whiteford James , D’Acquisto Fulvio , Jones Gareth E. , Rowe David , Nourshargh Sussan
Published: May 2012

Neutrophil transmigration through venular walls that are composed of endothelial cells (ECs), pericytes, and the venular basement membrane is a key component of innate immunity. Through direct analysis of leukocyte–pericyte interactions in inflamed tissues using confocal intravital microscopy, we show how pericytes facilitate transmigration in vivo. After EC migration, neutrophils crawl along pericyte processes to gaps between adjacent pericytes in an ICAM-1–, Mac-1–, and LFA-1–dependent manner. These gaps were enlarged in inflamed tissues through pericyte shape change and were used as exit points by neutrophils in breaching the venular wall. The findings identify previously unknown roles for pericytes in neutrophil transmigration in vivo and add additional steps to the leukocyte adhesion cascade that supports leukocyte trafficking into sites of inflammation.
Expression of the zinc finger transcription factor zDC (Zbtb46, Btbd4) defines the classical dendritic cell lineage
Authors: Meredith Matthew M. , Liu Kang , Darrasse-Jeze Guillaume , Kamphorst Alice O. , Schreiber Heidi A. , Guermonprez Pierre , Idoyaga Juliana , Cheong Cheolho , Yao Kai-Hui , Niec Rachel E. , Nussenzweig Michel C.
Published: May 2012

Classical dendritic cells (cDCs), monocytes, and plasmacytoid DCs (pDCs) arise from a common bone marrow precursor (macrophage and DC progenitors [MDPs]) and express many of the same surface markers, including CD11c. We describe a previously uncharacterized zinc finger transcription factor, zDC (Zbtb46, Btbd4), which is specifically expressed by cDCs and committed cDC precursors but not by monocytes, pDCs, or other immune cell populations. We inserted diphtheria toxin (DT) receptor (DTR) cDNA into the 3′ UTR of the zDC locus to serve as an indicator of zDC expression and as a means to specifically deplete cDCs. Mice bearing this knockin express DTR in cDCs but not other immune cell populations, and DT injection into zDC-DTR bone marrow chimeras results in cDC depletion. In contrast to previously characterized CD11c-DTR mice, non-cDCs, including pDCs, monocytes, macrophages, and NK cells, were spared after DT injection in zDC-DTR mice. We compared immune responses to Toxoplasma gondii and MO4 melanoma in DT-treated zDC- and CD11c-DTR mice and found that immunity was only partially impaired in zDC-DTR mice. Our results indicate that CD11c-expressing non-cDCs make significant contributions to initiating immunity to parasites and tumors.
Zbtb46 expression distinguishes classical dendritic cells and their committed progenitors from other immune lineages
Authors: Satpathy Ansuman T. , KC Wumesh , Albring Jörn C. , Edelson Brian T. , Kretzer Nicole M. , Bhattacharya Deepta , Murphy Theresa L. , Murphy Kenneth M.
Published: May 2012

Distinguishing dendritic cells (DCs) from other cells of the mononuclear phagocyte system is complicated by the shared expression of cell surface markers such as CD11c. In this study, we identified Zbtb46 (BTBD4) as a transcription factor selectively expressed by classical DCs (cDCs) and their committed progenitors but not by plasmacytoid DCs (pDCs), monocytes, macrophages, or other lymphoid or myeloid lineages. Using homologous recombination, we replaced the first coding exon of Zbtb46 with GFP to inactivate the locus while allowing detection of Zbtb46 expression. GFP expression in Zbtb46gfp/+ mice recapitulated the cDC-specific expression of the native locus, being restricted to cDC precursors (pre-cDCs) and lymphoid organ– and tissue-resident cDCs. GFP+ pre-cDCs had restricted developmental potential, generating cDCs but not pDCs, monocytes, or macrophages. Outside the immune system, Zbtb46 was expressed in committed erythroid progenitors and endothelial cell populations. Zbtb46 overexpression in bone marrow progenitor cells inhibited granulocyte potential and promoted cDC development, and although cDCs developed in Zbtb46gfp/gfp (Zbtb46 deficient) mice, they maintained expression of granulocyte colony-stimulating factor and leukemia inhibitory factor receptors, which are normally down-regulated in cDCs. Thus, Zbtb46 may help enforce cDC identity by restricting responsiveness to non-DC growth factors and may serve as a useful marker to identify rare cDC progenitors and distinguish between cDCs and other mononuclear phagocyte lineages.