bluuebunny/crossref_metadata_2025 huggingface dataset:
Propertiana
Authors: Trappes–Lomax John
Published: January 2012

The study of Propertius has been greatly facilitated by the publication by Stephen Heyworth of his Oxford Text and of his Cynthia. Many problems are now resolved or at any rate as near resolution as they are likely to be in the absence of some unexpected MS discovery. Other problems remain, and this very corrupt text will no doubt continue to provoke attempts at emendation; here are three. All citations are taken from Heyworth's OCT; references to comment by Heyworth are to his Cynthia.

Goold (1999) translates ‘the sea, locked out from shadowy Avernus’. Heyworth points out that since Agrippa's harbour works of 37 BC this was no longer the case, and that the meaning should be ‘enclosed by shady Avernus’. No doubt, but the natural meaning of claudo ab is' ‘to shut off from’; cf. Liv. 30.24.9 ea [insula] sinum ab alto claudit. The correct meaning can best be obtained by altering ab to in:

By opening up Avernus to sea-going vessels Agrippa has permitted the sea to enter the lake; cf. Suet. Aug. 16.1 portum Iulium apud Baias immisso in Lucrinum et Auernum lacum mari effecit; Verg. Geong. 2.164 Tyrrhenusque fretis immittitur aestus Auernis. The corruption could either be a trivial accident or else the deliberate work of a literal-minded scribe who could not see why it should be desirable to have the sea disporting itself inside a harbour.
Horace and historians
Authors: Woodman A. J.
Published: January 2012

In ‘the only coherent piece of autobiography which we possess from Horace's pen’, as Fraenkel has called it, the poet wrote these famous lines (Epist.2.2.49–52):

unde simul primum me dimisere Philippi,

decisis humilem pinnis inopemque paterni 50

et laris et fundi paupertas impulit audax

ut uersus facerem.

As soon as Philippi discharged me thence, poverty drove me grounded as I was, with my wings clipped, and deprived of my ancestral home and farm—boldly to produce verses.

As is remarked by Lyne, however, ‘Horace here omits an intervening and prosaic stage’. The evidence for this omission comes from Suetonius' biography of the poet, in which the same period of Horace's life is described slightly differently: ‘uictisque partibus uenia impetrata scriptum quaestorium comparauit. ac primo Maecenati … insinuatus…’ (‘after the defeat of his party and a successful request for pardon he procured the position ofscriba quaestorius. And having first become involved with Maecenas…’). What was the exact sequence of events? Lyne, like Brink, proposes that Horace after Philippi derived income from his position asscriba quacstoriusand that this in turn enabled him to write the poetry which eventually brought him to Maecenas' attention. Nisbet, on the other hand, thinks that Horace's early poetry elicited subsidies from ‘grandees like Pollio and Messalla’ and that these provided him with the wherewithal to buy his position asscriba, from which he was effectively relieved by his later association with Maecenas.
‘Collectors’ as stakeholders in Mycenaean governance: property and the relations between the ruling class and the state
Authors: Kyriakidis E.
Published: January 2012

There is a considerable body of literature concerned with the clarification of the role of the so-called ‘collectors’ in Mycenaean administration. In this article, a new interpretation will be proposed that offers a possible solution to the major points of dispute in the debate. This new interpretation has far-reaching consequences for our views of Mycenaean governance.

Although previous research has been summarized several times elsewhere—most recently and efficiently by Lupack (2008, 86–96) and before her by Bennet (1992, 65–89), we shall here review the key themes which are of particular relevance to the interpretation proposed below.
Writing and self-conscious mythopoiēsis in Euripides
Authors: Torrance Isabelle
Published: January 2012

Euripides uses a variety of strategies to draw attention to the novelties in his dramatic myth-creation ormythopoiēsis. He does so, for example, through multiple allusions to earlier poets, distinguishing himself from predecessors by acknowledging their influence while simultaneously producing something distinctive. Euripidean novelties are legitimized in several instances through cultic aetiologies. These aspects of Euripidean drama have long been acknowledged. More recently, Matthew Wright has shown how the characters in several Euripidean plays discuss their own myths in a self-conscious manner, a process he terms ‘metamythology’. A technique which has been less studied, however, is Euripides' exploration of the motif of writing and its connection to the act ofmythopoiēsiswithin his work. Scholars who discuss writing in Euripides have done so either within the general context of inherent tensions between oral and written communication in Greek tragedy (or Greek literature), or have focused on the use of letters as dramatic devices. This paper argues that Euripides exploits the motif of writing in a way which is entirely different from the other tragedians, and puts forward the central thesis that writing in Euripides is associated self-consciously and metapoetically with plot construction and authorial control.
First detection of O2 1.27 μm nightglow emission at Mars with OMEGA/MEX and comparison with general circulation model predictions
Authors: Bertaux J. L. , Gondet B. , Lefèvre F. , Bibring J. P. , Montmessin F.
Published: January 2012

We report the first detection in the atmosphere of Mars of the nightside O2(a1Δg) emission at 1.27 μm from limb observations of the OMEGA imaging spectrometer on board Mars Express (MEX). The emission, detected in three cases out of 40 observations, is due to recombination in a downwelling air parcel of O atoms produced by photodissociation of CO2 on the dayside in the upper atmosphere (O + O + M→ O2* + M), and not from ozone UV photodissociation, as is often seen on the dayside. Observed vertical profiles and total retrieved vertical intensities are compared with models. When detected, the emission is 10 times larger than previous predictions, at ∼240 kR. This can be explained in the frame of a general circulation model (GCM) of Mars. As predicted by the GCM, all positive observations were obtained at high latitudes, during the winter night. The model is validated, which simulates the large Hadley cell characterizing the meridional circulation, ascending from the summer pole and descending to the winter pole. This new emission is tracing uniquely a downward advection transport mechanism, and therefore its detailed study will provide important constraints on the overall aeronomy and dynamics of Mars. The impact on long‐term stability of methane is examined. It is found that recycling through the mesosphere will not decrease significantly the overall lifetime of CH4 (∼300 years), because the descent of air is confined to high latitudes and winter seasons. These observations are demonstrating a new diagnosis of the aeronomy and atmospheric dynamics of Mars.
Displacement fields from point cloud data: Application of particle imaging velocimetry to landslide geodesy
Authors: Aryal Arjun , Brooks Benjamin A. , Reid Mark E. , Bawden Gerald W. , Pawlak Geno R.
Published: January 2012

Acquiring spatially continuous ground‐surface displacement fields from Terrestrial Laser Scanners (TLS) will allow better understanding of the physical processes governing landslide motion at detailed spatial and temporal scales. Problems arise, however, when estimating continuous displacement fields from TLS point‐clouds because reflecting points from sequential scans of moving ground are not defined uniquely, thus repeat TLS surveys typically do not track individual reflectors. Here, we implemented the cross‐correlation‐based Particle Image Velocimetry (PIV) method to derive a surface deformation field using TLS point‐cloud data. We estimated associated errors using the shape of the cross‐correlation function and tested the method's performance with synthetic displacements applied to a TLS point cloud. We applied the method to the toe of the episodically active Cleveland Corral Landslide in northern California using TLS data acquired in June 2005–January 2007 and January–May 2010. Estimated displacements ranged from decimeters to several meters and they agreed well with independent measurements at better than 9% root mean squared (RMS) error. For each of the time periods, the method provided a smooth, nearly continuous displacement field that coincides with independently mapped boundaries of the slide and permits further kinematic and mechanical inference. For the 2010 data set, for instance, the PIV‐derived displacement field identified a diffuse zone of displacement that preceded by over a month the development of a new lateral shear zone. Additionally, the upslope and downslope displacement gradients delineated by the dense PIV field elucidated the non‐rigid behavior of the slide.
Sediment capture by vegetation patches: Implications for desertification and increased resource redistribution
Authors: Field Jason P. , Breshears David D. , Whicker Jeffrey J. , Zou Chris B.
Published: January 2012

Desertification impacts a large proportion of drylands and can be driven by a variety of climate and land use factors. Most conceptual models of desertification include the underlying assumption that when herbaceous cover is reduced, increased erosion from bare patches is redistributed to shrub canopy patches, resulting in self‐reinforcing “islands of fertility.” Notably, however, this underlying assumption has not been explicitly tested with direct field measurements. Here we provide direct measurements of horizontal sediment flux moving into and out of bare‐, herbaceous‐, and shrub‐dominated patch types in a semiarid ecosystem for both simulated and natural dust events, as well as in response to simulated disturbance. Horizontal sediment flux out of the bare patches was ∼20% greater than the herbaceous patches and ∼50% greater than sediment flux out of the shrub‐dominated patches. Differences among vegetation patch types indicate that shrub patches capture more sediment than herbaceous patches and, importantly, that bare patches serve as amplified sediment sources following disturbance. Our results provide explicit support for the pervasive but untested desertification redistribution assumption, highlighting that loss of grass cover is a compounding problem that not only increases dust emissions but also precludes capture, and may have global relevance for coupled human‐environmental systems at risk due to current or potential desertification.
Evidence of ferroelectricity and phase transition in pressed diphenylalanine peptide nanotubes
Authors: Bdikin Igor , Bystrov Vladimir , Kopyl Svitlana , Lopes Rui P. G. , Delgadillo Ivonne , Gracio José , Mishina Elena , Sigov Alexander , Kholkin Andrei L.
Published: January 2012

Self-assembled peptide nanotubes (PNT) are unique nanoscale objects having a great potential for a multitude of applications. Strong piezoactivity and polar properties in aromatic dipeptides were recently observed in stand-alone nanotubes using piezoresponse force microscopy and 2nd harmonic generation. In this work, we report macroscopic dielectric and polarization vs. field measurements on pressed PNTs before and after annealing at 150 °C. The results corroborate nanoscale study and present a clear evidence of ferroelectric-like behaviour and phase transition in this technologically important material. The dielectric constant of PNT pellets obeys apparent Curie-Weiss (CW) law with the CW constant C ≈ 230 °C and transition temperature at T ≈ 142 °C.
Free-energy analysis of the electron-density fluctuation in the quantum-mechanical/molecular-mechanical simulation combined with the theory of energy representation
Authors: Matubayasi Nobuyuki , Takahashi Hideaki
Published: January 2012

The relationship is investigated for QM/MM (quantum-mechanical/molecular-mechanical) systems between the fluctuations of the electronic state of the QM subsystem and of the solvation effect due to the QM-MM interaction. The free-energy change due to the electron-density fluctuation around its average is highlighted, and is evaluated through an approximate functional formulated in terms of distribution functions of the many-body coupling (pairwise non-additive) part of the QM-MM interaction energy. A set of QM/MM simulations are conducted in MM water solvent for QM water solute in ambient and supercritical conditions and for QM glycine solute in the neutral and zwitterionic forms. The variation of the electronic distortion energy of the QM solute in the course of QM/MM simulation is then shown to be compensated by the corresponding variation of the free energy of solvation. The solvation free energy conditioned by the electronic distortion energy is further analyzed with its components. It is found that the many-body contribution is essentially equal between the free energy and the average sum of solute-solvent interaction energy.
Effects of substrate orientation on the optical anisotropy spectra of GaN/AlN/Si heterostructures in the energy range from 2.0 to 3.5 eV
Authors: Lastras-Martínez L. F. , Balderas-Navarro R. E. , Herrera-Jasso R. , Ortega-Gallegos J. , Lastras-Martínez A. , Cordier Y. , Moreno J.-Ch. , Frayssinet E. , Semond F.
Published: January 2012

We report reflectance (R) and reflectance difference spectroscopy (RDS) spectra of wurtzite heterostructures grown on Si(111) and Si(110) substrates in the energy range from 2.0 to 3.5 eV. Due to the threefold symmetry of the Si(111) surface, the heterostructures grown on this surface will relax isotropically through the formation of misfit dislocations, preferably at the AlN/Si interface, and no in-plane anisotropies are expected. In fact, only a small in-plane anisotropy of reflectance is observed, due to the initial residual off-cut of the silicon substrate that leads to wurtzite layers with a c-axis slightly tilted with respect to the surface. In contrast, for the Si(110) substrate, strong differences in lattice parameters appear between silicon and GaN/AlN depending on the considered in-plane direction, leading to a large in-plane anisotropy. By using a multiple reflection model for R and the in-plane anisotropies described, we developed a model to describe the RDS spectra in the vicinity and below the fundamental gap of GaN.
Optical planar waveguide for cell counting
Authors: LeBlanc John , Mueller Andrew J. , Prinz Adrian , Butte Manish J.
Published: January 2012

Low cost counting of cells has medical applications in screening, military medicine, disaster medicine, and rural healthcare. In this report, we present a shallow, buried, planar waveguide fabricated by potassium ion exchange in glass that enables low-cost and rapid counting of metal-tagged objects that lie in the evanescent field of the waveguide. Laser light transmitted through the waveguide was attenuated proportionately to the presence of metal-coated microstructures fabricated from photoresist. This technology enables the low-cost enumeration of cells from blood, urine, or other biofluids.
In-line high efficient fiber polarizer based on surface plasmon
Authors: Dong Chun-Hua , Zou Chang-Ling , Ren Xi-Feng , Guo Guang-Can , Sun Fang-Wen
Published: January 2012

An in-line high efficient polarizer, composed of tapered fiber on the Au thin film, is theoretically proposed and experimentally demonstrated. The protocol is based on the high efficient adiabatic conversion of transverse magnetic mode from tapered fiber into surface plasmon (SP) and attenuates quickly in metal film. On the contrary, the transverse electric polarized light is influenced hardly in the whole process. The polarization extinction ratio higher than 500:1 (≈27 dB) is obtained in our experiment. Our demonstration offers a potential way to manipulate the polarization of light in integrated circuit and may inspirit more attention to surface plasmon based devices for polarization controlling.
Investigation of possible microcavity effect on lasing threshold of nonradiative-scattering-dominated semiconductor lasers
Authors: Kumar Sushil , Hu Qing
Published: January 2012

The effect of enhanced rate of spontaneous emission on gain and lasing threshold of semiconductor microcavity lasers has not been discussed clearly. Some reports have suggested that the lasing threshold in microcavities could possibly be lowered due to the so-called Purcell effect. Here, we argue that gain in weakly coupled semiconductor cavities is a local phenomenon, which occurs due to stimulated emission induced by an electromagnetic excitation and remains unaffected by the cavity boundary conditions. Hence, the Purcell effect in microcavities filled uniformly with a gain medium should not lead to a reduction in the laser’s threshold pump density, provided radiative scattering is not the dominant relaxation mechanism in the excited state. A systematic experimental investigation of laser threshold in parallel-plate semiconductor microcavity terahertz quantum-cascade lasers of different dimensions was found to be in accordance with our arguments.
Nanoscale diffraction imaging of the high-pressure transition in Fe1−xO
Authors: Ding Yang , Cai Zhonghou , Hu Qingyang , Sheng Hongwei , Chang Jun , Hemley Russell J. , Mao Wendy L.
Published: January 2012

To further understand the long-debated origin of the high-pressure cubic-rhombohedral transition in FeO, we investigated the domain wall structure in Fe0.94O using high-pressure microdiffraction imaging techniques. The results reveal a non-reflection type domain wall structure forming due to the cubic-rhombohedral transition in Fe0.94O, which suggests the transformation could be associated with defects and is unlikely to be ferroelastic in nature.
The bound states of Fe impurity in wurtzite GaN
Authors: Zhang M. , Zhou T. F. , Zhang Y. M. , Li B. , Zheng S. N. , Huang J. , Sun Y. P. , Ren G. Q. , Wang J. F. , Xu K. , Yang H.
Published: January 2012

A study on the bound states of Fe impurities in GaN by ultraviolet photoluminescence (PL) emissions is presented. Two elusive PL lines were observed at 3.463 eV (L1) and 3.447 eV (L2), respectively. The intensities of the two lines are proportional to the Fe concentration. The temperature dependence of L1 and L2 revealed acceptor-like and strong localized characteristic, respectively. Furthermore, Raman analysis indicated that L2 is correlated to an exciton bound to a nitride-vacancy (VN) related complex, i.e., [Fe2+-VN]. By co-doping with Si, the [Fe2+-VN]-related bound state will enable the spin-coupling between isolated iron ions.
Confined one-way mode at magnetic domain wall for broadband high-efficiency one-way waveguide, splitter and bender
Authors: Zhang Xiaogang , Li Wei , Jiang Xunya
Published: January 2012

We find the one-way mode (OWM) can be well-confined at the magnetic domain wall by the photonic bandgap of gyromagnetic bulk material. Utilizing the well-confined one-way mode at the domain wall, we demonstrate the photonic one-way waveguide, splitter and bender can be realized with simple structures, which are predicted to be high-efficiency, broadband, frequency-independent, reflection-free, crosstalk-proof, and robustness against disorder. Additionally, we find that the splitter and bender in our proposal can be transformed into each other with magnetic control, which may have great potential applications in all photonic integrated circuit.
Spectrally resolved size-dependent third-order nonlinear optical properties of colloidal CdSe quantum dots
Authors: Nyk M. , Wawrzynczyk D. , Szeremeta J. , Samoc M.
Published: January 2012

Nonlinear absorption and nonlinear refraction of colloidal CdSe quantum dots (QDs) of two sizes were investigated in a wide spectral range with the Z-scan technique using a tunable femtosecond laser system. The nonlinear absorption was found to be the strongest close to twice the wavelength of the second exciton absorption band of the QDs. Based on nonlinear optical parameters the exciton binding energy has been determined. The current results are compared to the nonlinear properties of CdSe QDs presented in the literature. The features of this system relevant for multiphoton fluorescence microscopy applications are discussed.
Expression patterns of auxin-responsive genes during tomato flower pedicel abscission and potential effects of calcium
Authors: Zuo Xianhong , Xu Tao , Qi Mingfang , Lv Shuangshuang , Li Jinhong , Gao Song , Li Tianlai
Published: January 2012

This study aimed to determine the expression patterns of auxin (Aux/IAA)-responsive genes (ARG) during tomato flower pedicel abscission and the role of calcium in this auxin-mediated abscission. Most of the 19 proteins encoded by SlIAA genes showed the presence of all four conserved domains (I, II, III and IV). Expressions of some SlIAA genes decreased significantly (SlIAA 1, 3, 5, 8, 9, 10, 16, 17 and 27), while others increased (SlIAA 2, 4, 6, 7, 11, 12, 13, 26 and 29) at 0.5 h after excision. Most SlIAA genes were significantly upregulated at 1 h (except 9 and 27) then decreased to relatively low levels until 4 h after excision (except 4, 5, 8, 12, 14, 26 and 29). The SIAA genes were analysed and screened based on their expression patterns during different abscission phases. SlIAA4, 6, 9, 12 and 27 had relatively high expression levels consistent with the abscission rate, indicating potential roles in mediating abscission. SlIAA2, 3, 4, 5, 7, 9, 12, 13, 14, 16, 17, 26, 27 and 29 may have been important in delaying abscission, while SlIAA1, 9 and 12 may have been required for the completion of ethylene-induced abscission. SlIAA4, 6, 7, 8, 14, 16, 17 and 29 were important in calcium-delayed abscission. Analysis of other ARG revealed that tomato GH3 may have acted as an effective negative regulator in IAA-induced delay in abscission, while small auxin-up RNA expression patterns indicated that it may be a marker of IAA level throughout the abscission process.
Antiangiogenic agents increase breast cancer stem cells via the generation of tumor hypoxia
Authors: Conley Sarah J. , Gheordunescu Elizabeth , Kakarala Pramod , Newman Bryan , Korkaya Hasan , Heath Amber N. , Clouthier Shawn G. , Wicha Max S.
Published: January 2012

Antiangiogenic therapy has been thought to hold significant potential for the treatment of cancer. However, the efficacy of such treatments, especially in breast cancer patients, has been called into question, as recent clinical trials reveal only limited effectiveness of antiangiogenic agents in prolonging patient survival. New research using preclinical models further suggests that antiangiogenic agents actually increase invasive and metastatic properties of breast cancer cells. We demonstrate that by generating intratumoral hypoxia in human breast cancer xenografts, the antiangiogenic agents sunitinib and bevacizumab increase the population of cancer stem cells. In vitro studies revealed that hypoxia-driven stem/progenitor cell enrichment is primarily mediated by hypoxia-inducible factor 1α. We further show that the Akt/β-catenin cancer stem cell regulatory pathway is activated in breast cancer cells under hypoxic conditions in vitro and in sunitinib-treated mouse xenografts. These studies demonstrate that hypoxia-driven cancer stem cell stimulation limits the effectiveness of antiangiogenic agents, and suggest that to improve patient outcome, these agents might have to be combined with cancer stem cell-targeting drugs.
Thrombospondin-1 acts as a ligand for CD148 tyrosine phosphatase
Authors: Takahashi Keiko , Mernaugh Raymond L. , Friedman David B. , Weller Rebecca , Tsuboi Nobuo , Yamashita Hironobu , Quaranta Vito , Takahashi Takamune
Published: January 2012

CD148 is a receptor-type protein tyrosine phosphatase that is expressed in several cell types, including vascular endothelial cells and duct epithelial cells. Growing evidence demonstrates a prominent role for CD148 in negative regulation of growth factor signals, suppressing cell proliferation and transformation. However, its extracellular ligand(s) remain unknown. To identify the ligand(s) of CD148, we introduced HA-tagged CD148 into cultured endothelial cells and then isolated its interacting extracellular protein(s) by biotin surface labeling and subsequent affinity purifications. The binding proteins were identified by mass spectrometry. Here we report that soluble thrombospondin-1 (TSP1) binds to the extracellular part of CD148 with high affinity and specificity, and its binding increases CD148 catalytic activity, leading to dephosphorylation of the substrate proteins. Consistent with these findings, introduction of CD148 conferred TSP1-mediated inhibition of cell growth to cells which lack CD148 and TSP1 inhibition of growth. Further, we demonstrate that TSP1-mediated inhibition of endothelial cell growth is antagonized by soluble CD148 ectodomain as well as by CD148 gene silencing. These findings provide evidence that CD148 functions as a receptor for TSP1 and mediates its inhibition of cell growth.
Use of red ochre by early Neandertals
Authors: Roebroeks Wil , Sier Mark J. , Nielsen Trine Kellberg , De Loecker Dimitri , Parés Josep Maria , Arps Charles E. S. , Mücher Herman J.
Published: January 2012

The use of manganese and iron oxides by late Neandertals is well documented in Europe, especially for the period 60–40 kya. Such finds often have been interpreted as pigments even though their exact function is largely unknown. Here we report significantly older iron oxide finds that constitute the earliest documented use of red ochre by Neandertals. These finds were small concentrates of red material retrieved during excavations at Maastricht-Belvédère, The Netherlands. The excavations exposed a series of well-preserved flint artifact (and occasionally bone) scatters, formed in a river valley setting during a late Middle Pleistocene full interglacial period. Samples of the reddish material were submitted to various forms of analyses to study their physical properties. All analyses identified the red material as hematite. This is a nonlocal material that was imported to the site, possibly over dozens of kilometers. Identification of the Maastricht-Belvédère finds as hematite pushes the use of red ochre by (early) Neandertals back in time significantly, to minimally 200–250 kya (i.e., to the same time range as the early ochre use in the African record).
Tracking energy transfer between light harvesting complex 2 and 1 in photosynthetic membranes grown under high and low illumination
Authors: Lüer Larry , Moulisová Vladimíra , Henry Sarah , Polli Dario , Brotosudarmo Tatas H. P. , Hoseinkhani Sajjad , Brida Daniele , Lanzani Guglielmo , Cerullo Giulio , Cogdell Richard J.
Published: January 2012

Energy transfer (ET) between B850 and B875 molecules in light harvesting complexes LH2 and LH1/RC (reaction center) complexes has been investigated in membranes of
Rhodopseudomonas palustris
grown under high- and low-light conditions. In these bacteria, illumination intensity during growth strongly affects the type of LH2 complexes synthesized, their optical spectra, and their amount of energetic disorder. We used a specially built femtosecond spectrometer, combining tunable narrowband pump with broadband white-light probe pulses, together with an analytical method based on derivative spectroscopy for disentangling the congested transient absorption spectra of LH1 and LH2 complexes. This procedure allows real-time tracking of the forward (LH2 → LH1) and backward (LH2←LH1) ET processes and unambiguous determination of the corresponding rate constants. In low-light grown samples, we measured lower ET rates in both directions with respect to high-light ones, which is explained by reduced spectral overlap between B850 and B875 due to partial redistribution of oscillator strength into a higher energetic exciton transition. We find that the low-light adaptation in
R. palustris
leads to a reduced elementary backward ET rate, in accordance with the low probability of two simultaneous excitations reaching the same LH1/RC complex under weak illumination. Our study suggests that backward ET is not just an inevitable consequence of vectorial ET with small energetic offsets, but is in fact actively managed by photosynthetic bacteria.
Adipose tissue-derived stem cell-seeded small intestinal submucosa for tunica albuginea grafting and reconstruction
Authors: Ma Limin , Yang Yijun , Sikka Suresh C. , Kadowitz Philip J. , Ignarro Louis J. , Abdel-Mageed Asim B. , Hellstrom Wayne J. G.
Published: January 2012

Porcine small intestinal submucosa (SIS) has been widely used in tunica albuginea (TA) reconstructive surgery. Adipose tissue-derived stem cells (ADSCs) can repair damaged tissue, augment cellular differentiation, and stimulate release of multiple growth factors. The aim of this rat study was to assess the feasibility of seeding ADSCs onto SIS grafts for TA reconstruction. Here, we demonstrate that seeding syngeneic ADSCs onto SIS grafts (SIS-ADSC) resulted in significant cavernosal tissue preservation and maintained erectile responses, similar to controls, in a rat model of bilateral incision of TA, compared with sham-operated animals and rats grafted with SIS graft (SIS) alone. In addition to increased TGF-β1 and FGF-2 expression levels, cross-sectional studies of the rat penis with SIS and SIS-ADSC revealed mild to moderate fibrosis and an increase of 30% and 40% in mean diameter in flaccid and erectile states, respectively. SIS grafting induced transcriptional up-regulation of iNOS and down-regulation of endothelial NOS, neuronal NOS, and VEGF, an effect that was restored by seeding ADCSs on the SIS graft. Taken together, these data show that rats undergoing TA incision with autologous SIS-ADSC grafts maintained better erectile function compared with animals grafted with SIS alone. This study suggests that SIS-ADSC grafting can be successfully used for TA reconstruction procedures and can restore erectile function.
Self-assembly of functional, amphipathic amyloid monolayers by the fungal hydrophobin EAS
Authors: Macindoe Ingrid , Kwan Ann H. , Ren Qin , Morris Vanessa K. , Yang Wenrong , Mackay Joel P. , Sunde Margaret
Published: January 2012

The hydrophobin EAS from the fungusNeurospora crassaforms functional amyloid fibrils called rodlets that facilitate spore formation and dispersal. Self-assembly of EAS into fibrillar rodlets occurs spontaneously at hydrophobic:hydrophilic interfaces and the rodlets further associate laterally to form amphipathic monolayers. We have used site-directed mutagenesis and peptide experiments to identify the region of EAS that drives intermolecular association and formation of the cross-β rodlet structure. Transplanting this region into a nonamyloidogenic hydrophobin enables it to form rodlets. We have also determined the structure and dynamics of an EAS variant with reduced rodlet-forming ability. Taken together, these data allow us to pinpoint the conformational changes that take place when hydrophobins self-assemble at an interface and to propose a model for the amphipathic EAS rodlet structure.
Effective guidance of collective migration based on differences in cell states
Authors: Inaki Mikiko , Vishnu Smitha , Cliffe Adam , Rørth Pernille
Published: January 2012

Directed cell migration is important for normal animal development and physiology. The process can also be subverted by tumor cells to invade other tissues and to metastasize. Some cells, such as leukocytes, migrate individually; other cells migrate together in groups or sheets, called collective cell migration. Guidance of individually migrating cells depends critically on subcellularly localized perception and transduction of signals. For collective cell migration, guidance could result from cells within a group achieving different signaling levels, with directionality then encoded in the collective rather than in individual cells. Here we subject this collective guidance hypothesis to direct tests, using migration of border cells during
Drosophila
oogenesis as our model system. These cells normally use two receptor tyrosine kinases (RTKs), PDGF/VEGF-related receptor (PVR) and EGFR, to read guidance cues secreted by the oocyte. Elevated but delocalized RTK signaling in one cell of the cluster was achieved by overexpression of PVR in the absence of ligand or by overexpression of fusion receptors unable to detect
Drosophila
ligands; alternatively, Rac was photoactivated centrally within a single cell. In each case, one cell within the group was in a high signal state, whereas others were in low signal states. The high signal cell directed cluster movement effectively. We conclude that differences in cell signaling states are sufficient to direct collective migration and are likely a substantial contributor to normal guidance. Cell signaling states could manifest as differences in gene expression or metabolite levels and thus differ substantially from factors normally considered when analyzing eukaryotic cell guidance.
Global kinetic analysis of proteolysis via quantitative targeted proteomics
Authors: Agard Nicholas J. , Mahrus Sami , Trinidad Jonathan C. , Lynn Aenoch , Burlingame Alma L. , Wells James A.
Published: January 2012

Mass spectrometry-based proteomics is a powerful tool for identifying hundreds to thousands of posttranslational modifications in complex mixtures. However, it remains enormously challenging to simultaneously assess the intrinsic catalytic efficiencies (
k
cat
/
K

M

) of these modifications in the context of their natural interactors. Such fundamental enzymological constants are key to determining substrate specificity and for establishing the timing and importance of cellular signaling. Here, we report the use of selected reaction monitoring (SRM) for tracking proteolysis induced by human apoptotic caspases-3, -7, -8, and -9 in lysates and living cells. By following the appearance of the cleaved peptides in lysate as a function of time, we were able to determine hundreds of catalytic efficiencies in parallel. Remarkably, we find the rates of substrate hydrolysis for individual caspases vary greater than 500-fold indicating a sequential process. Moreover, the rank-order of substrate cutting is similar in apoptotic cells, suggesting that cellular structures do not dramatically alter substrate accessibility. Comparisons of extrinsic (TRAIL) and intrinsic (staurosporine) inducers of apoptosis revealed similar substrate profiles, suggesting the final proteolytic demolitions proceed by similarly ordered plans. Certain biological processes were rapidly targeted by the caspases, including multiple components of the endocyotic pathway and miRNA processing machinery. We believe this massively parallel and quantitative label-free approach to obtaining basic enzymological constants will facilitate the study of proteolysis and other posttranslational modifications in complex mixtures.
DNA charge transport as a first step in coordinating the detection of lesions by repair proteins
Authors: Sontz Pamela A. , Mui Timothy P. , Fuss Jill O. , Tainer John A. , Barton Jacqueline K.
Published: January 2012

Damaged bases in DNA are known to lead to errors in replication and transcription, compromising the integrity of the genome. We have proposed a model where repair proteins containing redox-active [4Fe-4S] clusters utilize DNA charge transport (CT) as a first step in finding lesions. In this model, the population of sites to search is reduced by a localization of protein in the vicinity of lesions. Here, we examine this model using single-molecule atomic force microscopy (AFM). XPD, a 5′-3′ helicase involved in nucleotide excision repair, contains a [4Fe-4S] cluster and exhibits a DNA-bound redox potential that is physiologically relevant. In AFM studies, we observe the redistribution of XPD onto kilobase DNA strands containing a single base mismatch, which is not a specific substrate for XPD but, like a lesion, inhibits CT. We further provide evidence for DNA-mediated signaling between XPD and Endonuclease III (EndoIII), a base excision repair glycosylase that also contains a [4Fe-4S] cluster. When XPD and EndoIII are mixed together, they coordinate in relocalizing onto the mismatched strand. However, when a CT-deficient mutant of either repair protein is combined with the CT-proficient repair partner, no relocalization occurs. These data not only indicate a general link between the ability of a repair protein to carry out DNA CT and its ability to redistribute onto DNA strands near lesions but also provide evidence for coordinated DNA CT between different repair proteins in their search for damage in the genome.
Monoallelic silencing and haploinsufficiency in early murine intestinal neoplasms
Authors: Amos-Landgraf James M. , Irving Amy A. , Hartman Cory , Hunter Anthony , Laube Brianna , Chen Xiaodi , Clipson Linda , Newton Michael A. , Dove William F.
Published: January 2012

Studies of tumors from human familial adenomatous polyposis, sporadic colon cancer, and mouse and rat models of intestinal cancer indicate that the majority of early adenomas develop through loss of normal function of the
Adenomatous polyposis coli
(
APC
) gene. In murine models of familial adenomatous polyposis, specifically the multiple intestinal neoplasia mouse (Min) and the polyposis in the rat colon (Pirc) rat, most adenomas have lost their WT copy of the
Apc
gene through loss of heterozygosity by homologous somatic recombination. We report that large colonic adenomas in the
Pirc
rat have no detectable copy number losses or gains in genomic material and that most tumors lose heterozygosity only on the short arm of chromosome 18. Examination of early mouse and rat tumors indicates that a substantial subset of tumors shows maintenance of heterozygosity of
Apc
in genomic DNA, apparently violating Knudson's two-hit hypothesis. Sequencing of the
Apc
gene in a sampling of rat tumors failed to find secondary mutations in the majority of tumors that maintained heterozygosity of
Apc
in genomic DNA. Using quantitative allele-specific assays of
Apc
cDNA, we discovered two neoplastic pathways. One class of tumors maintains heterozygosity of
Apc

Min
/+

or

Apc
Pirc/+

RNA expression and may involve haploinsufficiency for Apc function. Another class of tumors exhibits highly biased monoallelic expression of the mutant
Apc
allele, providing evidence for a stochastic or random process of monoallelic epigenetic silencing of the tumor suppressor gene
Apc
.
Evidence for social working memory from a parametric functional MRI study
Authors: Meyer Meghan L. , Spunt Robert P. , Berkman Elliot T. , Taylor Shelley E. , Lieberman Matthew D.
Published: January 2012

Keeping track of various amounts of social cognitive information, including people's mental states, traits, and relationships, is fundamental to navigating social interactions. However, to date, no research has examined which brain regions support variable amounts of social information processing (“social load”). We developed a social working memory paradigm to examine the brain networks sensitive to social load. Two networks showed linear increases in activation as a function of increasing social load: the medial frontoparietal regions implicated in social cognition and the lateral frontoparietal system implicated in nonsocial forms of working memory. Of these networks, only load-dependent medial frontoparietal activity was associated with individual differences in social cognitive ability (trait perspective-taking). Although past studies of nonsocial load have uniformly found medial frontoparietal activity decreases with increasing task demands, the current study demonstrates these regions do support increasing mental effort when such effort engages social cognition. Implications for the etiology of clinical disorders that implicate social functioning and potential interventions are discussed.
Pyruvate kinase M2-specific siRNA induces apoptosis and tumor regression
Authors: Goldberg Michael S. , Sharp Phillip A.
Published: January 2012

The development of cancer-specific therapeutics has been limited because most healthy cells and cancer cells depend on common pathways. Pyruvate kinase (PK) exists in M1 (PKM1) and M2 (PKM2) isoforms. PKM2, whose expression in cancer cells results in aerobic glycolysis and is suggested to bestow a selective growth advantage, is a promising target. Because many oncogenes impart a common alteration in cell metabolism, inhibition of the M2 isoform might be of broad applicability. We show that several small interfering (si) RNAs designed to target mismatches between the M2 and M1 isoforms confer specific knockdown of the former, resulting in decreased viability and increased apoptosis in multiple cancer cell lines but less so in normal fibroblasts or endothelial cells. In vivo delivery of siPKM2 additionally causes substantial tumor regression of established xenografts. Our results suggest that the inherent nucleotide-level specificity of siRNA can be harnessed to develop therapeutics that target isoform-specific exons in genes exhibiting differential splicing patterns in various cell types.
Analysis of damping rate measurements of toroidal Alfvén eigenmodes on JET as a function of n: part I
Authors: Panis T. , Fasoli A. , Testa D.
Published: January 2012

The linear stability of Alfvén eigenmodes (AEs) is studied experimentally in the JET tokamak using its active MHD spectroscopy system, the so-called Alfvén Eigenmode Active Diagnostic (AEAD). Following the optimization of the AEAD system, AEs with toroidal mode numbers (n) in the low-n and medium-n range were excited systematically. A database was created from the damping rate measurements of toroidal AEs (TAEs), obtained in ohmically heated plasmas with monotonic q-profile. The TAE damping rate measurements were studied as a function of n, focusing on the effects of the edge plasma shape and the q profile and investigating their implications for the importance of the continuum and radiative damping mechanisms. In this paper, the first part of the analysis is presented: a statistical treatment of the damping rate database is performed and the correlations with various plasma parameters and relevant quantities are explored. The analysis shows that medium-n modes tend to be less damped than low-n modes, with the measured damping rates (γ/ω) of modes with n ⩾ 4 ranging from ∼0.3% to 4%. In a follow-up paper (part II), the analysis is carried out using a discharge-following approach, by investigating the damping rate variations that are observed in individual discharges.
Analysis of damping rate measurements of toroidal Alfvén eigenmodes as a function of n: part II
Authors: Panis T. , Fasoli A. , Testa D.
Published: January 2012

Complementing the database approach that has been presented in part I, this paper probes into individual plasma discharges and investigates the damping rate variations that are driven by the evolving plasma configurations. In addition to confirming the stabilizing effect of elongated plasma shapings on toroidal Alfvén eigenmodes, the significance of the span of the q profile is shown experimentally for the first time. It is found that, under conditions of transient current density profiles, the damping rate of medium-n modes has a dependence on the background plasma parameters that is distinctively different from that of low-n modes. The analysis of the correlation of the damping rate variations with the changes of the q profile shape and the alignment of the gaps of the shear Alfvén continuum leads to an assessment of the effect of the interaction of the modes with the Alfvén continuum as a function of n.
A Mutant in theADH1Gene ofChlamydomonas reinhardtiiElicits Metabolic Restructuring during Anaerobiosis
Authors: Magneschi Leonardo , Catalanotti Claudia , Subramanian Venkataramanan , Dubini Alexandra , Yang Wenqiang , Mus Florence , Posewitz Matthew C. , Seibert Michael , Perata Pierdomenico , Grossman Arthur R.
Published: January 2012

The green alga Chlamydomonas reinhardtii has numerous genes encoding enzymes that function in fermentative pathways. Among these, the bifunctional alcohol/acetaldehyde dehydrogenase (ADH1), highly homologous to the Escherichia coli AdhE enzyme, is proposed to be a key component of fermentative metabolism. To investigate the physiological role of ADH1 in dark anoxic metabolism, a Chlamydomonas  adh1 mutant was generated. We detected no ethanol synthesis in this mutant when it was placed under anoxia; the two other ADH homologs encoded on the Chlamydomonas genome do not appear to participate in ethanol production under our experimental conditions. Pyruvate formate lyase, acetate kinase, and hydrogenase protein levels were similar in wild-type cells and the adh1 mutant, while the mutant had significantly more pyruvate:ferredoxin oxidoreductase. Furthermore, a marked change in metabolite levels (in addition to ethanol) synthesized by the mutant under anoxic conditions was observed; formate levels were reduced, acetate levels were elevated, and the production of CO2 was significantly reduced, but fermentative H2 production was unchanged relative to wild-type cells. Of particular interest is the finding that the mutant accumulates high levels of extracellular glycerol, which requires NADH as a substrate for its synthesis. Lactate production is also increased slightly in the mutant relative to the control strain. These findings demonstrate a restructuring of fermentative metabolism in the adh1 mutant in a way that sustains the recycling (oxidation) of NADH and the survival of the mutant (similar to wild-type cell survival) during dark anoxic growth.
Adipokine profile in glucocorticoid‐treated patients: baseline plasma leptin level predicts occurrence of lipodystrophy
Authors: Fardet Laurence , Antuna‐Puente Barbara , Vatier Camille , Cervera Pascale , Touati Amel , Simon Tabassome , Capeau Jacqueline , Fève Bruno , Bastard Jean‐Philippe
Published: January 2012

Context

Glucocorticoid therapy may result in adipose tissue redistribution of unknown pathophysiology.

Objectives

To evaluate the effects of glucocorticoids on adipokine levels and adipose tissue inflammation. To compare the results in patients with or without glucocorticoid‐induced lipodystrophy (GIL) after 3 months of therapy.

Design and setting

Prospective monocentric study.

Patients

Adult patients initiating systemic, high‐dose prednisone therapy for at least 3 months. Blood samples and subcutaneous abdominal adipose tissue biopsies were collected at baseline and month 3. The presence of GIL after 3 months of therapy was assessed using standardized photography.

Results

Thirty‐two patients were enrolled. Blood samples and subcutaneous abdominal adipose tissue were available at baseline and month 3 for 30 patients [median age: 61 (38–79) years, 77% women]. Among those 30 patients, 15 were classified as GIL+ and 15 were GIL− at month 3. Between baseline and month 3, adiponectin and leptin levels increased in the overall population while the level of resistin remained unchanged. At baseline, leptin level was higher [19·3 (8·3–31·1) vs 4·5 (2·4–11·3) μg/l, P = 0·006] and resistin level lower [7·1 (6·3–12·4) vs 10·4 (8·0–21·7) μg/l, P = 0·05] in GIL+ than in GIL− patients. Baseline leptin level was predictive of GIL occurrence. Receiver operating characteristic curve analysis demonstrated that the best diagnostic accuracy was obtained with a baseline leptin cut‐off of 5·9 μg/l (sensitivity: 93%, specificity: 60%). At month 3, leptin and adiponectin levels increased more in the GIL+ than in the GIL− group, as did the number of anti‐inflammatory M2 macrophages in subcutaneous abdominal fat.

Conclusion

Glucocorticoid‐induced lipodystrophy is associated with a different adipokine profile both before and after glucocorticoid therapy. Serum leptin level prior to glucocorticoid therapy is highly predictive of GIL occurrence.