bluuebunny/crossref_metadata_2025 huggingface dataset:
Thermodynamics of supercooled water
Authors: Holten V. , Bertrand C. E. , Anisimov M. A. , Sengers J. V.
Published: March 2012

We review the available experimental information on the thermodynamic properties of supercooled water and demonstrate the possibility of modeling these thermodynamic properties on a theoretical basis. We show that by assuming the existence of a liquid–liquid critical point in supercooled water, the theory of critical phenomena can give an accurate account of the experimental thermodynamic-property data up to a pressure of 150 MPa. In addition, we show that a phenomenological extension of the theoretical model can account for all currently available experimental data in the supercooled region, up to 400 MPa. The stability limit of the liquid state and possible coupling between crystallization and liquid–liquid separation are also discussed. It is concluded that critical-point thermodynamics describes the available thermodynamic data for supercooled water within experimental accuracy, thus establishing a benchmark for further developments in this area.
Outer- and inner-valence satellites of carbon dioxide: Electron momentum spectroscopy compared with symmetry-adapted-cluster configuration interaction general-R calculations
Authors: Tian QiGuo , Yang Jing , Shi YuFeng , Shan Xu , Chen XiangJun
Published: March 2012

The extensive study of outer- and inner-valence satellites of carbon dioxide by electron momentum spectroscopy is reported. The experiments have been performed using a high-sensitivity electron momentum spectrometer employing non-coplanar symmetric geometry at impact energy of about 1200 eV. Binding energy spectrum up to 50 eV, above the first double ionization threshold (∼37.3 eV), is presented. Four main peaks and twelve satellites have been identified including four embedded in the double ionization continuum, among which the two beyond 42 eV are observed for the first time. High accuracy symmetry-adapted-cluster configuration interaction general-R calculation with aug-cc-pVTZ basis sets has also been performed and the result is in line with the experimental ionization spectrum except the relative intensities for some of the satellites in inner-valence region. The experimental momentum profiles for both the main ionization transitions and satellites have been obtained and compared with theoretical calculations by HF and B3LYP methods with 6-311++G* and aug-cc-pVTZ basis sets. Through comparison, the detailed assignments of the satellite bands have been achieved and the pole strengths for the relevant shake-up transitions are determined experimentally for the first time.
Hydrogen species motion in piezoelectrics: A quasi-elastic neutron scattering study
Authors: Alvine K. J. , Tyagi M. , Brown C. M. , Udovic T. J. , Jenkins T. , Pitman S. G.
Published: March 2012

Hydrogen is known to damage or degrade piezoelectric materials, at low pressure for ferroelectric random access memory applications, and at high pressure for hydrogen-powered vehicle applications. The piezoelectric degradation is in part governed by the motion of hydrogen species within the piezoelectric materials. We present here quasi-elastic neutron scattering (QENS) measurements of the local hydrogen species motion within lead zirconate titanate (PZT) and barium titanate (BTO) on samples charged by exposure to high-pressure gaseous hydrogen (≈17 MPa). Neutron vibrational spectroscopy (NVS) studies of the hydrogen-enhanced vibrational modes are presented as well. Results are discussed in the context of theoretically predicted interstitial hydrogen lattice sites and compared to comparable bulk diffusion studies of hydrogen diffusion in lead zirconate titanate.
A self-pumped high-temperature superconducting Josephson mixer: Modelling and measurement
Authors: Du J. , Macfarlane J. C. , Pegrum C. M. , Zhang T. , Cai Y. , Guo Y. J.
Published: March 2012

We have recently developed a high-temperature superconducting (HTS) Josephson self-pumped mixer with an on-chip heterodyne local oscillator. The device is based on HTS step-edge junction technology and a “resistive-superconducting quantum interference device” (RSQUID) configuration. The heterodyne local oscillator and mixer output are frequency-tunable from below 10 MHz to 5 GHz by a control current. The performance of the autonomous Josephson mixer–local oscillator has been experimentally evaluated in terms of the current-voltage characteristics, intermediate frequency (IF)-tunable bandwidth, operation range, linearity, bias current, and temperature dependence of the IF output (or mixer conversion efficiency). We find the results are in good overall agreement with numerical simulation.
Optical transition induced by molecular transformation in peptide nanostructures
Authors: Amdursky Nadav , Handelman Amir , Rosenman Gil
Published: March 2012

In this letter we present a variation in the optical properties of bio-organic peptide nanostructures, which are induced by molecular transformation. The self-assembled tubular structures are formed from short aromatic di-peptides. Upon thermal induction, the structure changes its molecular conformation, and the linear di-peptide closes into a cyclic peptide. This irreversible transition changes the molecular packing at the nanoscale, which results in reconstruction of the native quantum dot-like packing to quantum well-like packing and the generation of blue luminescence. We further show that the same cyclic peptide can exhibit different photoluminescence properties according to the formed structure.
Optimum strain configurations for carrier injection in near infrared Ge lasers
Authors: Aldaghri O. , Ikonić Z. , Kelsall R. W.
Published: March 2012

The behavior of direct and indirect valleys in Ge, and the bandgap shrinking, under different tensile-strain conditions in bulk Ge and Ge quantum well structures are explored using the deformation potential and k·p methods. The doping density required for filling the indirect valleys up to the Γ-valley is calculated for various strain and growth conditions, as well as the efficiency of electron injection into the Γ-valley, and the optimum cases for Ge laser operation are identified.
Temperature dependence of the indirect bandgap in ultrathin strained silicon on insulator layer
Authors: Munguía J. , Bluet J.-M. , Marty O. , Bremond G. , Mermoux M. , Rouchon D.
Published: March 2012

Photoluminescence spectroscopy is applied on tensely strained silicon on insulator layer in order to evaluate the temperature dependence of the indirect energy bandgap. The strained silicon indirect bandgap follows a similar behaviour to bulk silicon at high temperature (from 80 K up to 300 K) which was described from the Varshni [Physica 34, 149 (1967)] and Bose-Einstein equations. Nevertheless, at low temperature (from 9 K to 80 K), an unusual blueshift of the bandgap is evidenced. The latter can be modelled considering band-tail states of density of states which are related to the strain fluctuation.
Energies and transition wavelengths for Li II, Be III, B IV, C V embedded in Debye plasmas
Authors: Jiang Zishi , Kar Sabyasachi , Ho Y. K.
Published: March 2012

We have carried out non-relativistic calculations to investigate the effect of Debye plasmas screening on the doubly excited nonautoionizing 1,3Pe and 1,3Do states of Li II, Be III, B IV, and C V using highly correlated exponential wave functions within the framework of Ritz variational principle. The 2p2 3Pe, 2p3p 1Pe, and 2p3d 1,3Do states energies, and wavelengths for the 2p3p 1Pe → 2p3d 1Do, 2p2 3Pe→ 2p3d 3Do, 2p3p 3Pe → 2p3d 3Do, and 2p3p 3Pe → 2p3d 3Do transitions for different Debye lengths are reported. Comparisons are made with the existing results. Results for B IV and C V for different screening parameters are reported for the first time in the literature. Transition wavelengths show interesting behavior with increasing screening parameters and nuclear charge.
Experimental observation of radial breathing-like mode of graphene nanoribbons
Authors: Yu Fang , Zhou Haiqing , Zhang Zengxing , Tang Dongsheng , Chen Minjiang , Yang Huaichao , Wang Gang , Yang Haifang , Gu Changzhi , Sun Lianfeng
Published: March 2012

We report that single-walled carbon nanotubes (SWNTs) can be etched into graphene nanoribbons (GNRs) by iron etching, which is confirmed by Raman spectroscopy and transmission electron microscopy. Compared with SWNTs, there are some unique features in Raman spectra of GNRs: symmetric G peak with no splitting, larger Raman intensity of 2D peak than G peak, and lower frequency and narrower full width at half maximum for 2D peak. Similar to radial breathing modes in SWNTs, theoretically predicted radial breathing-like mode of GNRs is also observed: a clear and prominent peak around 223 cm−1 in the low frequency regions. This work paves the way for future studies of nanodevices based on SWNT-GNR heterojunction.
A simplicial gauge theory
Authors: Christiansen Snorre H. , Halvorsen Tore G.
Published: March 2012

We provide an action for gauge theories discretized on simplicial meshes, inspired by lattice gauge theory and finite element methods. The action is discretely gauge invariant and we give a proof of consistency. A discrete Noether's theorem that can be applied to our setting, is also proved.
Communication: Transition state theory for dissipative systems without a dividing surface
Authors: Revuelta F. , Bartsch Thomas , Benito R. M. , Borondo F.
Published: March 2012

Transition state theory is a central cornerstone in reaction dynamics. Its key step is the identification of a dividing surface that is crossed only once by all reactive trajectories. This assumption is often badly violated, especially when the reactive system is coupled to an environment. The calculations made in this way then overestimate the reaction rate and the results depend critically on the choice of the dividing surface. In this Communication, we study the phase space of a stochastically driven system close to an energetic barrier in order to identify the geometric structure unambiguously determining the reactive trajectories, which is then incorporated in a simple rate formula for reactions in condensed phase that is both independent of the dividing surface and exact.
Direct probing of selective electron and hole accumulation processes along the channel of an ambipolar double-layer field-effect transistor by optical modulation spectroscopy
Authors: Zhang Le , Taguchi Dai , Manaka Takaaki , Iwamoto Mitsumasa
Published: March 2012

By using optical modulation spectroscopy, the electronic state and selective carrier accumulation processes in the channel region of unipolar and ambipolar organic field effect transistors (OFETs) were directly probed. The modulated spectra of unipolar single-layer pentacene and C60 OFETs corresponding well with their I–V characteristics were understood in terms of the injected carrier induced effect. On the other hand, for the double-layer C60/pentacene OFETs, it is indicated that the modulated spectra under both hole and electron accumulation cases generated mainly from the pentacene layer but with different characteristics, implying that the injected carriers accumulated at spatially separated locations.
Multicolor Čerenkov conical beams generation by cascaded-χ(2) processes in radially poled nonlinear photonic crystals
Authors: Li H. X. , Mu S. Y. , Xu P. , Zhong M. L. , Chen C. D. , Hu X. P. , Cui W. N. , Zhu S. N.
Published: March 2012

We observe multiple simultaneous cascaded-χ(2) Čerenkov conical radiations in radially poled nonlinear photonic crystals. By using two incident fundamental waves ω1 and ω2, a variety of cascaded nonlinear up-conversion processes occur which result in high-frequency Čerenkov radiations at 2ωi+ωj(i,j=1,2) exhibiting as multicolor conical beams. Two types of phase-matching geometries with different emission angles are demonstrated for each kind of cascaded-χ(2) Čerenkov radiation. The external angle of the Čerenkov radiation exhibits strong dependence on the fundamental wavelengths. The experimental results agree well with the theoretical calculations.
Carrier dynamics and design optimization of electrolyte-induced inversion layer carbon nanotube-silicon Schottky junction solar cell
Authors: Chen Wenchao , Seol Gyungseon , Rinzler Andrew G. , Guo Jing
Published: March 2012

Carrier dynamics of the electrolyte-induced inversion layer carbon nanotube-silicon Schottky junction solar cells is explored by numerical simulations. Operation mechanisms of the solar cells with and without the electrolyte-induced inversion layer are presented and compared, which clarifies the current flow mechanisms in a solar cell with an induced inversion layer. A heavily doped back contact layer can behave as a hole block layer. In addition to lowering contact resistance and surface recombination, it is particularly useful for improving carrier separation in an electrolyte-induced inversion layer solar cell or a metal-insulator-semiconductor grating solar cell.
Is leaf pubescence of Cape Proteaceae a xeromorphic or radiation-protective trait?
Authors: Skelton R. P. , Midgley J. J. , Nyaga J. M. , Johnson S. D. , Cramer M. D.
Published: March 2012

Although pubescence has traditionally been considered to be related to the water economy of plants, the results are ambivalent and vary between different species. We tested two contrasting hypotheses for the functional significance of leaf pubescence of Proteaceae species from the Cape Floristic Region. First, we hypothesised that pubescence is a xeromorphic trait that conserves water by increasing the boundary layer resistance to diffusion. Water loss was measured in two morphotypes of Leucospermum conocarpodendron (L.) Buek that differ in the degree of leaf pubescence, using both gas exchange and gravimetric techniques. Pubescence contributed less than 5% of total leaf resistance and pubescent leaves transpired at least as rapidly as glabrous leaves due to having larger numbers of small stomata per leaf area. Although pubescence was not associated with drier sites in L. conocarpodendron, there was a weak negative correlation between rainfall and pubescence across 18 other Proteaceae species. We also hypothesised that pubescence is a radiation-protective trait. We assessed the effect of pubescence on light reflectance, leaf temperature, fluorescence and gas exchange characteristics in situ. Pubescent leaves of L. conocarpodendron were 19.2 ± 0.08% more reflective than glabrous leaves and had significantly greater pre-dawn photochemical efficiency. There was a positive association between leaf pubescence and habitat temperature in Proteaceae. We conclude that although pubescence is unlikely to be a xeric adaptation, it could serve a role in reducing photoinhibition and heat loading in Proteaceae species.
Responses to low phosphorus in high and low foliar anthocyanin coleus (Solenostemon scutellarioides) and maize (Zea mays)
Authors: Henry Amelia , Chopra Surinder , Clark David G. , Lynch Jonathan P.
Published: March 2012

Foliar anthocyanin production is frequently induced by phosphorus deficiency, but the adaptive significance of increased anthocyanin production under P stress, if any, remains unknown. In this study we hypothesised that if anthocyanin expression is an adaptive response to mitigate the stress effects of P deficiency, genotypes with constitutive anthocyanin expression would have greater tolerance to P stress than low anthocyanin-producing genotypes. Four studies were conducted in greenhouse, outdoor chamber and field conditions to compare genetically similar maize and coleus plants with contrasting anthocyanin accumulation (i.e. ‘red-leafed’ vs ‘green-leafed’). In low-P treatments, anthocyanin production did not consistently result in greater photosynthesis or biomass. In coleus, red-leafed phenotypes showed lower chlorophyll a/b ratios suggesting photoprotection by anthocyanins against degradation of light harvesting complex proteins. However, the opposite trend was observed in maize, where red-leafed phenotypes showed greater chlorophyll a/b ratios and lower qP (oxidation state of PSII). Based on results from the various treatments and growth conditions of this study, it could not be concluded that high foliar anthocyanin production confers a general functional advantage under low-P stress. More research comparing inducible vs constitutive production may help elucidate the role of anthocyanin biosynthesis in P deficiency responses.
Redescription of the western desert taipan, Oxyuranus temporalis (Serpentes:Elapidae), with notes on its distribution, diet and genetic variation
Authors: Brennan Karl E. C. , Morley Terry , Hutchinson Mark , Donnellan Steve
Published: March 2012

Of the three species of taipan, Oxyuranus temporalis is the least known, being described only recently from a single juvenile specimen. We redescribe the species based on additional adult specimens from the Great Victoria Desert. Molecular genetic variation between the three localities from which the species is known was low, suggesting a single widespread population or recent radiation. Limited analysis of faecal material and gut contents suggested solely mammalian prey. The additional specimens suggest the possibility of a considerable distribution across sandy deserts of the central and western interior of Australia. Further studies and fieldwork are required to more accurately determine its geographic range, quantify the toxicity of the venom and assess the suitability of available antivenoms.
Evidence from central Mexico supporting the Younger Dryas extraterrestrial impact hypothesis
Authors: Israde-Alcántara Isabel , Bischoff James L. , Domínguez-Vázquez Gabriela , Li Hong-Chun , DeCarli Paul S. , Bunch Ted E. , Wittke James H. , Weaver James C. , Firestone Richard B. , West Allen , Kennett James P. , Mercer Chris , Xie Sujing , Richman Eric K. , Kinzie Charles R. , Wolbach Wendy S.
Published: March 2012

We report the discovery in Lake Cuitzeo in central Mexico of a black, carbon-rich, lacustrine layer, containing nanodiamonds, microspherules, and other unusual materials that date to the early Younger Dryas and are interpreted to result from an extraterrestrial impact. These proxies were found in a 27-m-long core as part of an interdisciplinary effort to extract a paleoclimate record back through the previous interglacial. Our attention focused early on an anomalous, 10-cm-thick, carbon-rich layer at a depth of 2.8 m that dates to 12.9 ka and coincides with a suite of anomalous coeval environmental and biotic changes independently recognized in other regional lake sequences. Collectively, these changes have produced the most distinctive boundary layer in the late Quaternary record. This layer contains a diverse, abundant assemblage of impact-related markers, including nanodiamonds, carbon spherules, and magnetic spherules with rapid melting/quenching textures, all reaching synchronous peaks immediately beneath a layer containing the largest peak of charcoal in the core. Analyses by multiple methods demonstrate the presence of three allotropes of nanodiamond: n-diamond, i-carbon, and hexagonal nanodiamond (lonsdaleite), in order of estimated relative abundance. This nanodiamond-rich layer is consistent with the Younger Dryas boundary layer found at numerous sites across North America, Greenland, and Western Europe. We have examined multiple hypotheses to account for these observations and find the evidence cannot be explained by any known terrestrial mechanism. It is, however, consistent with the Younger Dryas boundary impact hypothesis postulating a major extraterrestrial impact involving multiple airburst(s) and and/or ground impact(s) at 12.9 ka.
Evolutionary dynamics of
Staphylococcus aureus
during progression from carriage to disease
Authors: Young Bernadette C. , Golubchik Tanya , Batty Elizabeth M. , Fung Rowena , Larner-Svensson Hanna , Votintseva Antonina A. , Miller Ruth R. , Godwin Heather , Knox Kyle , Everitt Richard G. , Iqbal Zamin , Rimmer Andrew J. , Cule Madeleine , Ip Camilla L. C. , Didelot Xavier , Harding Rosalind M. , Donnelly Peter , Peto Tim E. , Crook Derrick W. , Bowden Rory , Wilson Daniel J.
Published: March 2012

Whole-genome sequencing offers new insights into the evolution of bacterial pathogens and the etiology of bacterial disease.
Staphylococcus aureus
is a major cause of bacteria-associated mortality and invasive disease and is carried asymptomatically by 27% of adults. Eighty percent of bacteremias match the carried strain. However, the role of evolutionary change in the pathogen during the progression from carriage to disease is incompletely understood. Here we use high-throughput genome sequencing to discover the genetic changes that accompany the transition from nasal carriage to fatal bloodstream infection in an individual colonized with methicillin-sensitive
S. aureus
. We found a single, cohesive population exhibiting a repertoire of 30 single-nucleotide polymorphisms and four insertion/deletion variants. Mutations accumulated at a steady rate over a 13-mo period, except for a cluster of mutations preceding the transition to disease. Although bloodstream bacteria differed by just eight mutations from the original nasally carried bacteria, half of those mutations caused truncation of proteins, including a premature stop codon in an
AraC
-family transcriptional regulator that has been implicated in pathogenicity. Comparison with evolution in two asymptomatic carriers supported the conclusion that clusters of protein-truncating mutations are highly unusual. Our results demonstrate that bacterial diversity in vivo is limited but nonetheless detectable by whole-genome sequencing, enabling the study of evolutionary dynamics within the host. Regulatory or structural changes that occur during carriage may be functionally important for pathogenesis; therefore identifying those changes is a crucial step in understanding the biological causes of invasive bacterial disease.
Actin-dependent rapid recruitment of reluctant synaptic vesicles into a fast-releasing vesicle pool
Authors: Lee Jae Sung , Ho Won-Kyung , Lee Suk-Ho
Published: March 2012

Glutamatergic synaptic terminals harbor reluctant synaptic vesicles (SVs) that contribute little to synchronous release during action potentials but are release competent when stimulated by sucrose or by direct intracellular application of calcium. It has been noted that the proximity of a release-competent SV to the calcium source is one of the primary factors that differentiate reluctant SVs from fast-releasing ones at the calyx of Held synapse. It has not been known whether reluctant SVs can be converted into fast-releasing ones. Here we show that reluctant SVs are recruited rapidly in an actin-dependent manner to become fast-releasing SVs once the pool of fast-releasing SVs is depleted by a short depolarization. Recovery of the pool of fast-releasing SVs was accompanied by a parallel reduction in the number of reluctant SVs. Quantitative analysis of the time course of depletion of fast-releasing SVs during high-frequency stimulation revealed that in the early phase of stimulation reluctant SVs are converted rapidly into fast-releasing ones, thereby counteracting short-term depression. During the late phase, however, after reluctant vesicles have been used up, another process of calmodulin-dependent recruitment of fast-releasing SVs is activated. These results document that reluctant SVs have a role in short-term plasticity and support the hypothesis of positional priming, which posits that reluctant vesicles are converted into fast-releasing ones via relocation closer to Ca
2+
-channels.
Temporally tuned neuronal differentiation supports the functional remodeling of a neuronal network in
Drosophila
Authors: Veverytsa Lyubov , Allan Douglas W.
Published: March 2012

During insect metamorphosis, neuronal networks undergo extensive remodeling by restructuring their connectivity and recruiting newborn neurons from postembryonic lineages. The neuronal network that directs the essential behavior, ecdysis, generates a distinct behavioral sequence at each developmental transition. Larval ecdysis replaces the cuticle between larval stages, and pupal ecdysis externalizes and expands the head and appendages to their adult position. However, the network changes that support these differences are unknown. Crustacean cardioactive peptide (CCAP) neurons and the peptide hormones they secrete are critical for ecdysis; their targeted ablation alters larval ecdysis progression and results in a failure of pupal ecdysis. In this study, we demonstrate that the CCAP neuron network is remodeled immediately before pupal ecdysis by the emergence of 12 late CCAP neurons. All 12 are CCAP efferents that exit the central nervous system. Importantly, these late CCAP neurons were found to be entirely sufficient for wild-type pupal ecdysis, even after targeted ablation of all other 42 CCAP neurons. Our evidence indicates that late CCAP neurons are derived from early, likely embryonic, lineages. However, they do not differentiate to express their peptide hormone battery, nor do they project an axon via lateral nerve trunks until pupariation, both of which are believed to be critical for the function of CCAP efferent neurons in ecdysis. Further analysis implicated ecdysone signaling via ecdysone receptors A/B1 and the nuclear receptor ftz-f1 as the differentiation trigger. These results demonstrate the utility of temporally tuned neuronal differentiation as a hard-wired developmental mechanism to remodel a neuronal network to generate a scheduled change in behavior.
F1Fo-ATPase, F-type proton-translocating ATPase, at the plasma membrane is critical for efficient influenza virus budding
Authors: Gorai Takeo , Goto Hideo , Noda Takeshi , Watanabe Tokiko , Kozuka-Hata Hiroko , Oyama Masaaki , Takano Ryo , Neumann Gabriele , Watanabe Shinji , Kawaoka Yoshihiro
Published: March 2012

The identification of host factors involved in virus replication is important to understand virus life cycles better. Accordingly, we sought host factors that interact with the influenza viral nonstructural protein 2 by using coimmunoprecipitation followed by mass spectrometry. Among proteins associating with nonstructural protein 2, we focused on the β subunit of the F1Fo-ATPase, which received a high probability score in our mass spectrometry analysis. The siRNA-mediated down-regulation of the β subunit of the F1Fo-ATPase reduced influenza virion formation and virus growth in cell culture. We further found that efficient influenza virion formation requires the ATPase activity of F1Fo-ATPase and that plasma membrane-associated, but not mitochondrial, F1Fo-ATPase is important for influenza virion formation and budding. Hence, our data identify plasma membrane-associated F1Fo-ATPase as a critical host factor for efficient influenza virus replication.
Early ontogenic origin of the hematopoietic stem cell lineage
Authors: Tanaka Yosuke , Hayashi Misato , Kubota Yasushi , Nagai Hiroki , Sheng Guojun , Nishikawa Shin-Ichi , Samokhvalov Igor M.
Published: March 2012

Several lines of evidence suggest that the adult hematopoietic system has multiple developmental origins, but the ontogenic relationship between nascent hematopoietic populations under this scheme is poorly understood. In an alternative theory, the earliest definitive blood precursors arise from a single anatomical location, which constitutes the cellular source for subsequent hematopoietic populations. To deconvolute hematopoietic ontogeny, we designed an embryo-rescue system in which the key hematopoietic factor Runx1 is reactivated in Runx1-null conceptuses at specific developmental stages. Using complementary in vivo and ex vivo approaches, we provide evidence that definitive hematopoiesis and adult-type hematopoietic stem cells originate predominantly in the nascent extraembryonic mesoderm. Our data also suggest that other anatomical sites that have been proposed to be sources of the definitive hematopoietic hierarchy are unlikely to play a substantial role in de novo blood generation.
Defining the molecular interface that connects the Fanconi anemia protein FANCM to the Bloom syndrome dissolvasome
Authors: Hoadley Kelly A. , Xue Yutong , Ling Chen , Takata Minoru , Wang Weidong , Keck James L.
Published: March 2012

The RMI subcomplex (RMI1/RMI2) functions with the BLM helicase and topoisomerase IIIα in a complex called the “dissolvasome,” which separates double-Holliday junction DNA structures that can arise during DNA repair. This activity suppresses potentially harmful sister chromatid exchange (SCE) events in wild-type cells but not in cells derived from Bloom syndrome patients with inactivating
BLM
mutations. The RMI subcomplex also associates with FANCM, a component of the Fanconi anemia (FA) core complex that is important for repair of stalled DNA replication forks. The RMI/FANCM interface appears to help coordinate dissolvasome and FA core complex activities, but its precise role remains poorly understood. Here, we define the structure of the RMI/FANCM interface and investigate its roles in coordinating cellular DNA-repair activities. The X-ray crystal structure of the RMI core complex bound to a well-conserved peptide from FANCM shows that FANCM binds to both RMI proteins through a hydrophobic “knobs-into-holes” packing arrangement. The RMI/FANCM interface is shown to be critical for interaction between the components of the dissolvasome and the FA core complex. FANCM variants that substitute alanine for key interface residues strongly destabilize the complex in solution and lead to increased SCE levels in cells that are similar to those observed in
blm
- or
fancm
-deficient cells. This study provides a molecular view of the RMI/FANCM complex and highlights a key interface utilized in coordinating the activities of two critical eukaryotic DNA-damage repair machines.
Lipophilic analogs of zoledronate and risedronate inhibit
Plasmodium
geranylgeranyl diphosphate synthase (GGPPS) and exhibit potent antimalarial activity
Authors: No Joo Hwan , de Macedo Dossin Fernando , Zhang Yonghui , Liu Yi-Liang , Zhu Wei , Feng Xinxin , Yoo Jinyoung Anny , Lee Eunhae , Wang Ke , Hui Raymond , Freitas-Junior Lucio H. , Oldfield Eric
Published: March 2012

We report the results of an in vitro screening assay targeting the intraerythrocytic form of the malaria parasite
Plasmodium falciparum
using a library of 560 prenyl-synthase inhibitors. Based on “growth-rescue” and enzyme-inhibition experiments, geranylgeranyl diphosphate synthase (GGPPS) is shown to be a major target for the most potent leads, BPH-703 and BPH-811, lipophilic analogs of the bone-resorption drugs zoledronate and risedronate. We determined the crystal structures of these inhibitors bound to a
Plasmodium
GGPPS finding that their head groups bind to the [Mg
2+
]
3
cluster in the active site in a similar manner to that found with their more hydrophilic parents, whereas their hydrophobic tails occupy a long-hydrophobic tunnel spanning both molecules in the dimer. The results of isothermal-titration-calorimetric experiments show that both lipophilic bisphosphonates bind to GGPPS with, on average, a ΔG of -9 kcal mol
-1
, only 0.5 kcal mol
-1
worse than the parent bisphosphonates, consistent with the observation that conversion to the lipophilic species has only a minor effect on enzyme activity. However, only the lipophilic species are active in cells. We also tested both compounds in mice, finding major decreases in parasitemia and 100% survival. These results are of broad general interest because they indicate that it may be possible to overcome barriers to cell penetration of existing bisphosphonate drugs in this and other systems by simple covalent modification to form lipophilic analogs that retain their enzyme-inhibition activity and are also effective in vitro and in vivo.
A unified framework for non-Brownian suspension flows and soft amorphous solids
Authors: Lerner Edan , Düring Gustavo , Wyart Matthieu
Published: March 2012

While the rheology of non-Brownian suspensions in the dilute regime is well understood, their behavior in the dense limit remains mystifying. As the packing fraction of particles increases, particle motion becomes more collective, leading to a growing length scale and scaling properties in the rheology as the material approaches the jamming transition. There is no accepted microscopic description of this phenomenon. However, in recent years it has been understood that the elasticity of simple amorphous solids is governed by a critical point, the unjamming transition where the pressure vanishes, and where elastic properties display scaling and a diverging length scale. The correspondence between these two transitions is at present unclear. Here we show that for a simple model of dense flow, which we argue captures the essential physics near the jamming threshold, a formal analogy can be made between the rheology of the flow and the elasticity of simple networks. This analogy leads to a new conceptual framework to relate microscopic structure to rheology. It enables us to define and compute numerically normal modes and a density of states. We find striking similarities between the density of states in flow, and that of amorphous solids near unjamming: both display a plateau above some frequency scale
ω
∗
 ∼ |
z
c
 - 
z
|, where
z
is the coordination of the network of particle in contact,
z
c
 = 2
D
where
D
is the spatial dimension. However, a spectacular difference appears: the density of states in flow displays a single mode at another frequency scale
ω
min
 ≪ 
ω
∗
governing the divergence of the viscosity.
Silencing of parathyroid hormone (PTH) receptor 1 in T cells blunts the bone anabolic activity of PTH
Authors: Bedi Brahmchetna , Li Jau-Yi , Tawfeek Hesham , Baek Ki-Hyun , Adams Jonathan , Vangara Sameera S. , Chang Ming-Kang , Kneissel Michaela , Weitzmann M. Neale , Pacifici Roberto
Published: March 2012

Intermittent parathyroid hormone (iPTH) treatment stimulates T-cell production of the osteogenic Wnt ligand Wnt10b, a factor required for iPTH to activate Wnt signaling in osteoblasts and stimulate bone formation. However, it is unknown whether iPTH induces Wnt10b production and bone anabolism through direct activation of the parathyroid hormone (PTH)/PTH-related protein receptor (PPR) in T cells. Here, we show that conditional silencing of PPR in T cells blunts the capacity of iPTH to induce T-cell production of Wnt10b; activate Wnt signaling in osteoblasts; expand the osteoblastic pool; and increase bone turnover, bone mineral density, and trabecular bone volume. These findings demonstrate that direct PPR signaling in T cells plays an important role in PTH-induced bone anabolism by promoting T-cell production of Wnt10b and suggest that T cells may provide pharmacological targets for bone anabolism.
Population bulk segregant mapping uncovers resistance mutations and the mode of action of a chitin synthesis inhibitor in arthropods
Authors: Van Leeuwen Thomas , Demaeght Peter , Osborne Edward J. , Dermauw Wannes , Gohlke Simon , Nauen Ralf , Grbić Miodrag , Tirry Luc , Merzendorfer Hans , Clark Richard M.
Published: March 2012

Because of its importance to the arthropod exoskeleton, chitin biogenesis is an attractive target for pest control. This point is demonstrated by the economically important benzoylurea compounds that are in wide use as highly specific agents to control insect populations. Nevertheless, the target sites of compounds that inhibit chitin biogenesis have remained elusive, likely preventing the full exploitation of the underlying mode of action in pest management. Here, we show that the acaricide etoxazole inhibits chitin biogenesis in
Tetranychus urticae
(the two-spotted spider mite), an economically important pest. We then developed a population-level bulk segregant mapping method, based on high-throughput genome sequencing, to identify a locus for monogenic, recessive resistance to etoxazole in a field-collected population. As supported by additional genetic studies, including sequencing across multiple resistant strains and genetic complementation tests, we associated a nonsynonymous mutation in the major
T. urticae
chitin synthase (
CHS1
) with resistance. The change is in a C-terminal transmembrane domain of CHS1 in a highly conserved region that may serve a noncatalytic but essential function. Our finding of a target-site resistance mutation in
CHS1
shows that at least one highly specific chitin biosynthesis inhibitor acts directly to inhibit chitin synthase. Our work also raises the possibility that other chitin biogenesis inhibitors, such as the benzoylurea compounds, may also act by inhibition of chitin synthases. More generally, our genetic mapping approach should be powerful for high-resolution mapping of simple traits (resistance or otherwise) in arthropods.
Incorporation of new information into prefrontal cortical activity after learning working memory tasks
Authors: Meyers Ethan M. , Qi Xue-Lian , Constantinidis Christos
Published: March 2012

The ability to learn new tasks requires that new information is integrated into neural systems that already support other behaviors. To study how new information is incorporated into neural representations, we analyzed single-unit recordings from the prefrontal cortex (PFC), a brain region important for task acquisition and working memory, before and after monkeys learned to perform two behavioral tasks. A population-decoding analysis revealed a large increase in task-relevant information, and smaller changes in stimulus-related information, after training. This new information was contained in dynamic patterns of neural activity, with many individual neurons containing the new task-relevant information for only relatively short periods of time in the midst of other large firing rate modulations. Additionally, we found that stimulus information could be decoded with high accuracy only from dorsal PFC, whereas task-relevant information was distributed throughout both dorsal and ventral PFC. These findings help resolve a controversy about whether PFC is innately specialized to process particular types of information or whether its responses are completely determined by task demands by showing there is both regional specialization within PFC that was present before training, as well as more widespread task-relevant information that is a direct result of learning. The results also show that information is incorporated into PFC through the emergence of a small population of highly selective neurons that overlay new signals on top of patterns of activity that contain information about previously encoded variables, which gives insight into how information is coded in neural activity.
Looking backwards to move forwards: Charlotte Mason on history
Authors: Cooper Hilary
Published: March 2012

It has been suggested that the new National Curriculum for history in primary schools should focus on content and on knowing the dates of English kings and queens rather than on the process of historical enquiry, in order to promote a shared sense of identity. Charlotte Mason was a very patriotic, nineteenth‐century British educationalist who saw learning history as not Anglocentric and as an active engagement with primary and secondary sources, in order to interpret the past through retelling, role play and art. This article collates her thoughts about history education scattered throughout six volumes of her writing.
Potential for excellence: interdisciplinary learning outdoors as a moral enterprise
Authors: Allison Pete , Carr David , Meldrum George
Published: March 2012

This article is concerned with the place and status of outdoor learning within formal schooling. In light of recent British outdoor educational trends, it considers the general educational significance of outdoor learning in the context of the recent Scottish Curriculum for Excellence. The article begins with an overview of some key educational concerns, and – drawing on the philosophies of Aristotle and Dewey – some discussion of the educational significance of interdisciplinary teaching and learning. The empirical component of the article focuses on visits to schools and outdoor education centres to explore teachers' understandings of, beliefs about and values concerning outdoor learning. The article relates these views to the philosophies of Aristotle and Dewey and to outdoor learning understood as an essentially interdisciplinary moral enterprise. It concludes by exploring some possible practical and curricular implications of teachers' views in light of the Curriculum for Excellence.
Educational change in Scotland: policy, context and biography
Authors: Priestley M. , Miller K.
Published: March 2012

The poor success rate of policy for curriculum change has been widely noted in the educational change literature. Part of the problem lies in the complexity of schools, as policy‐makers have proven unable to micro‐manage the multifarious range of factors that impact upon the implementation of policy. This article draws upon empirical data from a local authority‐led initiative to implement Scotland%s new National Curriculum. It offers a set of conceptual tools derived from critical realism (particularly the work of Margaret Archer), which offer significant potential in allowing us to develop greater understanding of the complexities of educational change. Archer%s social theory developed as a means of explaining change and continuity in social settings. As schools and other educational institutions are complex social organisations, critical realism offers us methodological tools for tracking the ebbs and flows of change cycles over time, presenting the means for mapping the multifarious networks and assemblages that form their basis.
David, Mr Bear and Bernstein: searching for an equitable pedagogy through guided group work
Authors: Boyle Bill , Charles Marie
Published: March 2012

The authors' experiences of observing teaching and learning in schools have led them to become concerned at the dominant paradigm of a ‘pedagogy of poverty' at the expense of a ‘pedagogy of plenty'. Bernstein%s theory of power and control of education knowledge is overtly practised in classrooms globally. This is evidenced in the narrowing of the curriculum in response to the ‘No Child Left Behind' initiative in the USA and the centrally imposed National Strategies and Standards agenda in the UK. Bernstein%s theory is still a means of clarifying the relationships between social class, family income and the education process. It introduced the concept of ‘restricted and elaborated codes', which has been labelled by its critics as a deficit model for the working‐class population. The authors contest that expectations for this new meritocracy have failed to materialise and the expectations for equity have been reduced by the prevailing metric. This ‘pedagogy of poverty' is now practised in the current ‘one size fits all' model of teaching and learning operating within narrow accountability based on a ‘testocracy'. This case study demonstrates one teacher using guided group work as a potential strategy for a ‘pedagogy of plenty'.
My Word! Interference from Reading Object Names Implies a Role for Competition during Picture Name Retrieval
Authors: Vitkovitch Melanie , Cooper Elisa
Published: March 2012

A related word prime has been found to interfere with picture naming after unrelated intervening trials (word-to-picture interference). Recently, Stroop-type picture–word interference effects have been interpreted in terms of a postlexical response exclusion process rather than a competitive lexical selection process. An experiment is reported that examines whether word-to-picture effects could reflect response exclusion mechanisms and, more generally, strategic processing of the word prime. Forty-eight volunteer university students named aloud sequences of semantically related (and unrelated) word primes and picture targets, separated by two unrelated filler stimuli. On half of the trials, participants were asked to count backwards in threes from a random number presented immediately after naming the prime word. They were also given a surprise recall test at the end of the naming block. Results for naming times and errors indicated a main effect of relatedness; semantic interference effects were not dependent on the unfilled gap following the word prime trial and were also not tied to episodic recall of prime words. The data indicate that slowed picture naming times are more likely to emerge from processes intrinsic to word prime naming rather than controlled processing and do not readily fit the postlexical response exclusion account. The results are considered in relation to two recent accounts of interference over unrelated trials, which refer to some form of competition at, or prior to, lexical access.
Drosophila CK1-γ, gilgamesh, controls PCP-mediated morphogenesis through regulation of vesicle trafficking
Authors: Gault William J. , Olguin Patricio , Weber Ursula , Mlodzik Marek
Published: March 2012

Cellular morphogenesis, including polarized outgrowth, promotes tissue shape and function. Polarized vesicle trafficking has emerged as a fundamental mechanism by which protein and membrane can be targeted to discrete subcellular domains to promote localized protrusions. Frizzled (Fz)/planar cell polarity (PCP) signaling orchestrates cytoskeletal polarization and drives morphogenetic changes in such contexts as the vertebrate body axis and external Drosophila melanogaster tissues. Although regulation of Fz/PCP signaling via vesicle trafficking has been identified, the interplay between the vesicle trafficking machinery and downstream terminal PCP-directed processes is less established. In this paper, we show that Drosophila CK1-γ/gilgamesh (gish) regulates the PCP-associated process of trichome formation through effects on Rab11-mediated vesicle recycling. Although the core Fz/PCP proteins dictate prehair formation broadly, CK1-γ/gish restricts nucleation to a single site. Moreover, CK1-γ/gish works in parallel with the Fz/PCP effector multiple wing hairs, which restricts prehair formation along the perpendicular axis to Gish. Our findings suggest that polarized Rab11-mediated vesicle trafficking regulated by CK1-γ is required for PCP-directed processes.
JunB contributes to Id2 repression and the epithelial–mesenchymal transition in response to transforming growth factor–β
Authors: Gervasi Megan , Bianchi-Smiraglia Anna , Cummings Michael , Zheng Qiao , Wang Dan , Liu Song , Bakin Andrei V.
Published: March 2012

The process of epithelial–mesenchymal transition (EMT) in response to transforming growth factor–β (TGF-β) contributes to tissue fibrosis, wound healing, and cancer via a mechanism that is not fully understood. This study identifies a critical role of JunB in the EMT and profibrotic responses to TGF-β. Depletion of JunB by small interfering ribonucleic acid abrogates TGF-β–induced disruption of cell–cell junctions, formation of actin fibers, focal adhesions, and expression of fibrotic proteins. JunB contributes to Smad-mediated repression of inhibitor of differentiation 2 through interaction with transcription repressor activating transcription factor 3. Importantly, JunB mediates the TGF-β induction of profibrotic response factors, fibronectin, fibulin-2, tropomyosin (Tpm1), and integrin-β3, which play critical roles in matrix deposition, cell–matrix adhesion, and actin stress fibers. In summary, JunB provides important input in setting the transcriptional program of the EMT and profibrotic responses to TGF-β. Thus, JunB represents an important target in diseases associated with EMT, including cancer and fibrosis.