bluuebunny/crossref_metadata_2025 huggingface dataset:
Electronic transitions and fermi edge singularity in polar heterostructures studied by absorption and emission spectroscopy
Authors: Pandey S. , Cavalcoli D. , Minj A. , Fraboni B. , Cavallini A. , Gamarra P. , Poisson M. A.
Published: December 2012

Optically induced electronic transitions in nitride based polar heterostructures have been investigated by absorption and emission spectroscopy. Surface photovoltage (SPV), photocurrent (PC), and photo luminescence spectroscopy have been applied to high quality InAlN/AlN/GaN structures to study the optical properties of two dimensional electron gas. Energy levels within the two dimensional electron gas (2DEG) well at the interface between the GaN and AlN have been directly observed by SPV and PC. Moreover, a strong enhancement of the photoluminescence intensity due to holes recombining with electrons at the Fermi Energy, known as fermi energy singularity, has been observed. These analyses have been carried out on InAlN/AlN/GaN heterojunctions with the InAlN barrier layer having different In content, a parameter which affects the energy levels within the 2DEG well as well as the optical signal intensity. The measured energy values are in a very good agreement with the ones obtained by Schrödinger–Poisson simulations.
Optimum condition to fabricate 5–10 nm SiO2/Si structure using advanced nitric acid oxidation of Si method with Si source
Authors: Imamura Kentaro , Matsumoto Taketoshi , Kobayashi Hikaru
Published: December 2012

A low temperature (≦120 °C) fabrication method to form relatively thick SiO2/Si structure with a Si source has been developed using the advanced nitric acid oxidation of Si (NAOS) method, and the formation mechanism has been investigated. The reaction mechanism consists of direct oxidation of Si, dissolution of Si sources, and surface reaction of the dissolved Si species. The dissolved Si species is present in HNO3 solutions as mono-silicic acid and reacts with oxidizing species formed by decomposition of HNO3 on an ultrathin SiO2 layer (i.e., 1.4 nm) produced by the direct oxidation of Si substrates with HNO3 solutions. To achieve a uniform thickness of SiO2 layer with a smooth surface, HNO3 solutions with concentrations higher than 60 wt. % are needed because the dissolved Si species polymerizes in HNO3 solutions when the concentration is below 60 wt. %, resulting in the formation of SiO2 particles in HNO3, which are deposited afterwards on the SiO2 layer. In spite of the low temperature formation at 120 °C, the electrical characteristics of the advanced NAOS SiO2 layer formed with 68 wt. % HNO3 and subsequent post-metallization anneal at 250 °C are nearly identical to those of thermal oxide formed at 900 °C.
Quantum-dot density dependence of power conversion efficiency of intermediate-band solar cells
Authors: Sakamoto Katsuyoshi , Kondo Yasunori , Uchida Keisuke , Yamaguchi Koichi
Published: December 2012

For intermediate-band solar cells containing GaAs/InAs quantum dots (QDs), the QD density dependence of the power conversion efficiency (PCE) was theoretically calculated for various sun concentrations under AM1.5 conditions based on detailed balance principles. A QD density of over 5 × 1013 cm−2 was required to achieve a PCE of more than 50% under 10 000 suns. However, under the photo-filled state and 1 sun, the PCE decreased over a wide total QD density range from about 3 × 1010 to 1 × 1013 cm−2. This reduction was attributed to the negative net carrier generation rate through the intermediate band, which was due to insufficient two-step optical absorption. The short-circuit current density increased as the QD density increased up to about 1 × 1011 cm−2 and it then saturated. In contrast, the open-circuit voltage decreased with increasing QD density. This reduction in the open-circuit voltage was suppressed at high sun concentrations.
Rapid distortion analysis of high Mach number homogeneous shear flows: Characterization of flow-thermodynamics interaction regimes
Authors: Bertsch Rebecca L. , Suman Sawan , Girimaji Sharath S.
Published: December 2012

In high-speed shear flows the nature of flow-thermodynamics interactions, and consequently the character of transition/turbulence, changes markedly with Mach number. We identify and characterize three different regimes of interactions in terms of acoustic frequency-to-shear magnitude ratio employing the linear rapid distortion analysis. We begin with an analysis of the pressure equation and demonstrate that acoustic frequency grows monotonically with time in this initial value problem whereas the shear magnitude is imposed to be constant. Initially when acoustic frequency is smaller than shear magnitude, fluctuations grow rapidly as the velocity field evolves unrestrained by pressure. This corresponds to Regime 1 wherein there is no significant flow-thermodynamics interaction. Flow-thermodynamics interactions commence in Regime 2 as acoustic frequency grows to the level of imposed shear rate. Dilatational velocity and pressure fields in the flow-normal direction are generated. The two fields are coupled as in a simple harmonic oscillator and consequently shear stresses oscillate about a near zero value. Thus production is drastically reduced leading to stabilization of perturbation kinetic energy growth rate. Further increase in acoustic frequency beyond shear magnitude leads to Regime 3. The solenoidal perturbations begin to dominate the flow statistics and the kinetic energy evolution bears much semblance to the incompressible shear flow. Overall, this work leads to improved insight into high-speed shear flow physics.
Quantum vortex reconnections
Authors: Zuccher S. , Caliari M. , Baggaley A. W. , Barenghi C. F.
Published: December 2012

We study reconnections of quantum vortices by numerically solving the governing Gross-Pitaevskii equation. We find that the minimum distance between vortices scales differently with time before and after the vortex reconnection. We also compute vortex reconnections using the Biot-Savart law for vortex filaments of infinitesimal thickness, and find that, in this model, reconnections are time symmetric. We argue that the likely cause of the difference between the Gross-Pitaevskii model and the Biot-Savart model is the intense rarefaction wave which is radiated away from a Gross-Pitaeveskii reconnection. Finally we compare our results to experimental observations in superfluid helium and discuss the different length scales probed by the two models and by experiments.
Molecular orientation and photoswitching kinetics on single-walled carbon nanotubes by optical second harmonic generation
Authors: McGee David J. , Huang Changshui , Kim Myungwoong , Choi Jonathan W. , Eriksson Mark A. , Gopalan Padma
Published: December 2012

Electrical conduction through chromophore-functionalized nanotubes can be modulated by light with wavelengths expected to isomerize the chromophores. Here, we use second harmonic generation to directly measure the orientation and photoisomerization kinetics of azo-benzene chromophores on single-walled carbon nanotubes. We find a net chromophore orientation with an average chromophore tilt angle of 40° ± 3°. We show that this angle can be reduced effectively to zero with an applied corona field. Periodic illumination with unpolarized 495 nm light induces reversible trans-cis switching, enabling the extraction of switching time scales both with and without an applied electric field.
Breakup and coalescence characteristics of a hollow cone swirling spray
Authors: Saha Abhishek , Lee Joshua D. , Basu Saptarshi , Kumar Ranganathan
Published: December 2012

This paper deals with an experimental study of the breakup characteristics of water emanating from hollow cone hydraulic injector nozzles induced by pressure-swirling. The experiments were conducted using two nozzles with different orifice diameters 0.3 mm and 0.5 mm and injection pressures (0.3–4 MPa) which correspond to Rep = 7000–26 000. Two types of laser diagnostic techniques were utilized: shadowgraph and phase Doppler particle anemometry for a complete study of the atomization process. Measurements that were made in the spray in both axial and radial directions indicate that both velocity and average droplet diameter profiles are highly dependent on the nozzle characteristics, Weber number and Reynolds number. The spatial variation of diameter and velocity arises principally due to primary breakup of liquid films and subsequent secondary breakup of large droplets due to aerodynamic shear. Downstream of the nozzle, coalescence of droplets due to collision was also found to be significant. Different types of liquid film breakup were considered and found to match well with the theory. Secondary breakup due to shear was also studied theoretically and compared to the experimental data. Coalescence probability at different axial and radial locations was computed to explain the experimental results. The spray is subdivided into three zones: near the nozzle, a zone consisting of film and ligament regime, where primary breakup and some secondary breakup take place; a second zone where the secondary breakup process continues, but weakens, and the centrifugal dispersion becomes dominant; and a third zone away from the spray where coalescence is dominant. Each regime has been analyzed in detail, characterized by timescale and Weber number and validated using experimental data.
p-InGaN/AlGaN electron blocking layer for InGaN/GaN blue light-emitting diodes
Authors: Liu Zhiqiang , Ma Jun , Yi Xiaoyan , Guo Enqing , Wang Liancheng , Wang Junxi , Lu Na , Li Jinmin , Ferguson Ian , Melton Andrew
Published: December 2012

In this work, the advantages of the p-InGaN/AlGaN electron blocking layer (EBL) for InGaN/GaN light-emitting diodes (LEDs) were studied numerically and experimentally. The LEDs with p-InGaN/AlGaN EBL exhibited better optical performance over a wide range of carrier concentration due to the enhancement of holes' injection and electrons' confinement. The values of A, B, C, and D coefficients had been iteratively obtained by fitting quantum efficiency in the modified rate equation model. The analysis indicated that the improvement in the device properties could be attributed to the relatively small band gap and p-type doping of InGaN insertion layer.
Atmospheric-pressure guided streamers for liposomal membrane disruption
Authors: Svarnas P. , Matrali S. H. , Gazeli K. , Aleiferis Sp. , Clément F. , Antimisiaris S. G.
Published: December 2012

The potential to use liposomes (LIPs) as a cellular model in order to study interactions of cold atmospheric-pressure plasma with cells is herein investigated. Cold atmospheric-pressure plasma is formed by a dielectric-barrier discharge reactor. Large multilamellar vesicle liposomes, consisted of phosphatidylcholine and cholesterol, are prepared by the thin film hydration technique, to encapsulate a small hydrophilic dye, i.e., calcein. The plasma-induced release of calcein from liposomes is then used as a measure of liposome membrane integrity and, consequently, interaction between the cold atmospheric plasma and lipid bilayers. Physical mechanisms leading to membrane disruption are suggested, based on the plasma characterization including gas temperature calculation.
Non-perpendicular hypersonic and optical stop-bands in porous silicon multilayers
Authors: Manzanares-Martinez J. , Moctezuma-Enriquez D. , Rodriguez-Viveros Y. J. , Manzanares-Martinez B. , Castro-Garay P.
Published: December 2012

We study by theoretical simulations the non-perpendicular propagation of electromagnetic and elastic waves in porous silicon multilayers. We proceeded in three steps. First, we found the conditions to obtain a simultaneous photonic-phononic mirror at normal incidence. Second, we determined the angular variation of the mirrors computing the projected band structure. In a third step, we found out, on the one hand, that there are no conditions to obtain an omnidirectional mirror for electromagnetic waves. But, on the other hand, we found the conditions were possible to obtain an omnidirectional mirror for elastic waves. Moreover, the elastic mirror is revealed to be a polarization-converter due to the conversion of evanescent modes in the band gap.
Role of Al and Ti for ohmic contact formation in AlGaN/GaN heterostructures
Authors: Tokuda Hirokuni , Kojima Toshikazu , Kuzuhara Masaaki
Published: December 2012

A mechanism for ohmic contact formation using Ti/Al based metals on AlGaN/GaN heterostructures has been investigated by measuring temperature dependence of sheet electron density (ns) and mobility (μ). It was found that both ns and μ at room temperature for Ti/Al deposited sample were increased by annealing in vacuum, while not for Al/Ti deposited one. The results, especially increase in μ, cannot be understood by the conventional ohmic formation model, including Ti-N (nitrogen) complex formation or N vacancy formation. As the most probable mechanism for the increase in ns and μ, we have proposed a model, in which tensile strain is induced by the reaction of Ti/Al and AlGaN after annealing.
A continuous climatic impact on Holocene human population in the Rocky Mountains
Authors: Kelly Robert L. , Surovell Todd A. , Shuman Bryan N. , Smith Geoffrey M.
Published: December 2012

Ancient cultural changes have often been linked to abrupt climatic events, but the potential that climate can exert a persistent influence on human populations has been debated. Here, independent population, temperature, and moisture history reconstructions from the Bighorn Basin in Wyoming (United States) show a clear quantitative relationship spanning 13 ka, which explains five major periods of population growth/decline and ∼45% of the population variance. A persistent ∼300-y lag in the human demographic response conforms with either slow (∼0.3%) intrinsic annual population growth rates or a lag in the environmental carrying capacity, but in either case, the population continuously adjusted to changing environmental conditions.
Measuring collective transport by defined numbers of processive and nonprocessive kinesin motors
Authors: Furuta Ken’ya , Furuta Akane , Toyoshima Yoko Y. , Amino Misako , Oiwa Kazuhiro , Kojima Hiroaki
Published: December 2012

Intracellular transport is thought to be achieved by teams of motor proteins bound to a cargo. However, the coordination within a team remains poorly understood as a result of the experimental difficulty in controlling the number and composition of motors. Here, we developed an experimental system that links together defined numbers of motors with defined spacing on a DNA scaffold. By using this system, we linked multiple molecules of two different types of kinesin motors, processive kinesin-1 or nonprocessive Ncd (kinesin-14), in vitro. Both types of kinesins markedly increased their processivities with motor number. Remarkably, despite the poor processivity of individual Ncd motors, the coupling of two Ncd motors enables processive movement for more than 1 μm along microtubules (MTs). This improvement was further enhanced with decreasing spacing between motors. Force measurements revealed that the force generated by groups of Ncd is additive when two to four Ncd motors work together, which is much larger than that generated by single motors. By contrast, the force of multiple kinesin-1s depends only weakly on motor number. Numerical simulations and single-molecule unbinding measurements suggest that this additive nature of the force exerted by Ncd relies on fast MT binding kinetics and the large drag force of individual Ncd motors. These features would enable small groups of Ncd motors to crosslink MTs while rapidly modulating their force by forming clusters. Thus, our experimental system may provide a platform to study the collective behavior of motor proteins from the bottom up.
Electronic structure of the unique [4Fe-3S] cluster in O
2
-tolerant hydrogenases characterized by
57
Fe Mössbauer and EPR spectroscopy
Authors: Pandelia Maria-Eirini , Bykov Dmytro , Izsak Robert , Infossi Pascale , Giudici-Orticoni Marie-Thérèse , Bill Eckhard , Neese Frank , Lubitz Wolfgang
Published: December 2012

Iron–sulfur clusters are ubiquitous electron transfer cofactors in hydrogenases. Their types and redox properties are important for H
2
catalysis, but, recently, their role in a protection mechanism against oxidative inactivation has also been recognized for a [4Fe-3S] cluster in O
2
-tolerant group 1 [NiFe] hydrogenases. This cluster, which is uniquely coordinated by six cysteines, is situated in the proximity of the catalytic [NiFe] site and exhibits unusual redox versatility. The [4Fe-3S] cluster in hydrogenase (Hase) I from
Aquifex aeolicus
performs two redox transitions within a very small potential range, forming a superoxidized state above +200 mV vs. standard hydrogen electrode (SHE). Crystallographic data has revealed that this state is stabilized by the coordination of one of the iron atoms to a backbone nitrogen. Thus, the proximal [4Fe-3S] cluster undergoes redox-dependent changes to serve multiple purposes beyond classical electron transfer. In this paper, we present field-dependent
57
Fe-Mössbauer and EPR data for Hase I, which, in conjunction with spectroscopically calibrated density functional theory (DFT) calculations, reveal the distribution of Fe valences and spin-coupling schemes for the iron–sulfur clusters. The data demonstrate that the electronic structure of the [4Fe-3S] core in its three oxidation states closely resembles that of corresponding conventional [4Fe-4S] cubanes, albeit with distinct differences for some individual iron sites. The medial and distal iron–sulfur clusters have similar electronic properties as the corresponding cofactors in standard hydrogenases, although their redox potentials are higher.
Violating the Shannon capacity of metric graphs with entanglement
Authors: Briët Jop , Buhrman Harry , Gijswijt Dion
Published: December 2012

The Shannon capacity of a graph
G
is the maximum asymptotic rate at which messages can be sent with zero probability of error through a noisy channel with confusability graph
G
. This extensively studied graph parameter disregards the fact that on atomic scales, nature behaves in line with quantum mechanics. Entanglement, arguably the most counterintuitive feature of the theory, turns out to be a useful resource for communication across noisy channels. Recently [Leung D, Mančinska L, Matthews W, Ozols M, Roy A (2012)
Commun Math Phys
311:97–111], two examples of graphs were presented whose Shannon capacity is strictly less than the capacity attainable if the sender and receiver have entangled quantum systems. Here, we give natural, possibly infinite, families of graphs for which the entanglement-assisted capacity exceeds the Shannon capacity.
Persistent effects of a severe drought on Amazonian forest canopy
Authors: Saatchi Sassan , Asefi-Najafabady Salvi , Malhi Yadvinder , Aragão Luiz E. O. C. , Anderson Liana O. , Myneni Ranga B. , Nemani Ramakrishna
Published: December 2012

Recent Amazonian droughts have drawn attention to the vulnerability of tropical forests to climate perturbations. Satellite and in situ observations have shown an increase in fire occurrence during drought years and tree mortality following severe droughts, but to date there has been no assessment of long-term impacts of these droughts across landscapes in Amazonia. Here, we use satellite microwave observations of rainfall and canopy backscatter to show that more than 70 million hectares of forest in western Amazonia experienced a strong water deficit during the dry season of 2005 and a closely corresponding decline in canopy structure and moisture. Remarkably, and despite the gradual recovery in total rainfall in subsequent years, the decrease in canopy backscatter persisted until the next major drought, in 2010. The decline in backscatter is attributed to changes in structure and water content associated with the forest upper canopy. The persistence of low backscatter supports the slow recovery (>4 y) of forest canopy structure after the severe drought in 2005. The result suggests that the occurrence of droughts in Amazonia at 5–10 y frequency may lead to persistent alteration of the forest canopy.
Evidence for abundant isolated magnetic nanoparticles at the Paleocene–Eocene boundary
Authors: Wang Huapei , Kent Dennis V. , Jackson Michael J.
Published: December 2012

New rock magnetic results (thermal fluctuation tomography, high-resolution first-order reversal curves and low temperature measurements) for samples from the Paleocene–Eocene thermal maximum and carbon isotope excursion in cored sections at Ancora and Wilson Lake on the Atlantic Coastal Plain of New Jersey indicate the presence of predominantly isolated, near-equidimensional single-domain magnetic particles rather than the chain patterns observed in a cultured magnetotactic bacteria sample or magnetofossils in extracts. The various published results can be reconciled with the recognition that chain magnetosomes tend to be preferentially extracted in the magnetic separation process but, as we show, may represent only a small fraction of the overall magnetic assemblage that accounts for the greatly enhanced magnetization of the carbon isotope excursion sediment but whose origin is thus unclear.
Single-molecule analysis of fluorescently labeled G-protein–coupled receptors reveals complexes with distinct dynamics and organization
Authors: Calebiro Davide , Rieken Finn , Wagner Julia , Sungkaworn Titiwat , Zabel Ulrike , Borzi Alfio , Cocucci Emanuele , Zürn Alexander , Lohse Martin J.
Published: December 2012

G-protein–coupled receptors (GPCRs) constitute the largest family of receptors and major pharmacological targets. Whereas many GPCRs have been shown to form di-/oligomers, the size and stability of such complexes under physiological conditions are largely unknown. Here, we used direct receptor labeling with SNAP-tags and total internal reflection fluorescence microscopy to dynamically monitor single receptors on intact cells and thus compare the spatial arrangement, mobility, and supramolecular organization of three prototypical GPCRs: the β
1
-adrenergic receptor (β
1
AR), the β
2
-adrenergic receptor (β
2
AR), and the γ-aminobutyric acid (GABA
B
) receptor. These GPCRs showed very different degrees of di-/oligomerization, lowest for β
1
ARs (monomers/dimers) and highest for GABA
B
receptors (prevalently dimers/tetramers of heterodimers). The size of receptor complexes increased with receptor density as a result of transient receptor–receptor interactions. Whereas β
1
-/β
2
ARs were apparently freely diffusing on the cell surface, GABA
B
receptors were prevalently organized into ordered arrays, via interaction with the actin cytoskeleton. Agonist stimulation did not alter receptor di-/oligomerization, but increased the mobility of GABA
B
receptor complexes. These data provide a spatiotemporal characterization of β
1
-/β
2
ARs and GABA
B
receptors at single-molecule resolution. The results suggest that GPCRs are present on the cell surface in a dynamic equilibrium, with constant formation and dissociation of new receptor complexes that can be targeted, in a ligand-regulated manner, to different cell-surface microdomains.
Ecosystem variability and early human habitats in eastern Africa
Authors: Magill Clayton R. , Ashley Gail M. , Freeman Katherine H.
Published: December 2012

The role of savannas during the course of early human evolution has been debated for nearly a century, in part because of difficulties in characterizing local ecosystems from fossil and sediment records. Here, we present high-resolution lipid biomarker and isotopic signatures for organic matter preserved in lake sediments at Olduvai Gorge during a key juncture in human evolution about 2.0 Ma—the emergence and dispersal of
Homo erectus
(sensu lato). Using published data for modern plants and soils, we construct a framework for ecological interpretations of stable carbon-isotope compositions (expressed as
δ
13
C values) of lipid biomarkers from ancient plants. Within this framework,
δ
13
C values for sedimentary leaf lipids and total organic carbon from Olduvai Gorge indicate recurrent ecosystem variations, where open C
4
grasslands abruptly transitioned to closed C
3
forests within several hundreds to thousands of years. Carbon-isotopic signatures correlate most strongly with Earth’s orbital geometry (precession), and tropical sea-surface temperatures are significant secondary predictors in partial regression analyses. The scale and pace of repeated ecosystem variations at Olduvai Gorge contrast with long-held views of directional or stepwise aridification and grassland expansion in eastern Africa during the early Pleistocene and provide a local perspective on environmental hypotheses of human evolution.
Selective presynaptic enhancement of the prefrontal cortex to nucleus accumbens pathway by cocaine
Authors: Suska Anna , Lee Brian R. , Huang Yanhua H. , Dong Yan , Schlüter Oliver M.
Published: December 2012

The nucleus accumbens (NAc) regulates motivated behavior by, in part, processing excitatory synaptic projections from several brain regions. Among these regions, the prefrontal cortex (PFC) and basolateral amygdala, convey executive control and affective states, respectively. Whereas glutamatergic synaptic transmission within the NAc has been recognized as a primary cellular target for cocaine and other drugs of abuse to induce addiction-related pathophysiological motivational states, the understanding has been thus far limited to drug-induced postsynaptic alterations. It remains elusive whether exposure to cocaine or other drugs of abuse influences presynaptic functions of these excitatory projections, and if so, in which projection pathways. Using optogenetic methods combined with biophysical assays, we demonstrate that the presynaptic release probability (Pr) of the PFC-to-NAc synapses was enhanced after short-term withdrawal (1 d) and long-term (45 d) withdrawal from either noncontingent (i.p. injection) or contingent (self-administration) exposure to cocaine. After long-term withdrawal of contingent drug exposure, the Pr was higher compared with i.p. injected rats. In contrast, within the basolateral amygdala afferents, presynaptic Pr was not significantly altered in any of these experimental conditions. Thus, cocaine-induced procedure- and pathway-specific presynaptic enhancement of excitatory synaptic transmission in the NAc. These results, together with previous findings of cocaine-induced postsynaptic enhancement, suggest an increased PFC-to-NAc shell glutamatergic synaptic transmission after withdrawal from exposure to cocaine. This presynaptic alteration may interact with other cocaine-induced cellular adaptations to shift the functional output of NAc neurons, contributing to the addictive emotional and motivational state.
Field experiment estimate of electoral fraud in Russian parliamentary elections
Authors: Enikolopov Ruben , Korovkin Vasily , Petrova Maria , Sonin Konstantin , Zakharov Alexei
Published: December 2012

Electoral fraud is a widespread phenomenon, especially outside the developed world. Despite abundant qualitative and anecdotal evidence on its existence from around the world, there is very limited quantitative evidence on the extent of electoral fraud. We exploit random assignment of independent observers to 156 of 3,164 polling stations in the city of Moscow to estimate the effect of electoral fraud on the outcome of the Russian parliamentary elections held on December 4, 2011. We estimate the actual share of votes for the incumbent United Russia party to be at least 11 percentage points lower than the official count (36% instead of 47%). Our results suggest that the extent of the fraud was sufficient to have had a substantial impact on the outcome of the elections; they also confirm that the presence of observers is an important factor in ensuring the integrity of the procedure.
Deubiquitination of NF-κB by Ubiquitin-Specific Protease-7 promotes transcription
Authors: Colleran Amy , Collins Patricia E. , O’Carroll Christine , Ahmed Abrar , Mao Xicheng , McManus Bettina , Kiely Patrick A. , Burstein Ezra , Carmody Ruaidhrí J.
Published: December 2012

NF-κB is the master regulator of the immune response and is responsible for the transcription of hundreds of genes controlling inflammation and immunity. Activation of NF-κB occurs in the cytoplasm through the kinase activity of the IκB kinase complex, which leads to translocation of NF-κB to the nucleus. Once in the nucleus, NF-κB transcriptional activity is regulated by DNA binding-dependent ubiquitin-mediated proteasomal degradation. We have identified the deubiquitinase Ubiquitin Specific Protease-7 (USP7) as a regulator of NF-κB transcriptional activity. USP7 deubiquitination of NF-κB leads to increased transcription. Loss of USP7 activity results in increased ubiquitination of NF-κB, leading to reduced promoter occupancy and reduced expression of target genes in response to Toll-like– and TNF-receptor activation. These findings reveal a unique mechanism controlling NF-κB activity and demonstrate that the deubiquitination of NF-κB by USP7 is critical for target gene transcription.
CTLA-4 controls the thymic development of both conventional and regulatory T cells through modulation of the TCR repertoire
Authors: Verhagen Johan , Genolet Raphaël , Britton Graham J. , Stevenson Brian J. , Sabatos-Peyton Catherine A. , Dyson Julian , Luescher Immanuel F. , Wraith David C.
Published: December 2012

Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4; CD152) is of pivotal importance for self-tolerance, with deficiency or unfavorable polymorphisms leading to autoimmune disease. Tolerance to self-antigens is achieved through thymic deletion of highly autoreactive conventional T (Tconv) cells and generation of FoxP3+regulatory T (Treg) cells. The main costimulatory molecule, CD28, augments the negative selection of Tconv cells and promotes the generation of FoxP3+Treg cells. The role of its antagonistic homolog CTLA-4, however, remains a topic of debate. To address this topic, we investigated the thymic development of T cells in the presence and absence of CTLA-4 in a T-cell receptor (TCR) transgenic mouse model specific for the myelin basic protein peptide Ac1–9. We reveal that CTLA-4 is expressed in the corticomedullary region of the thymus. Its absence alters the response of CD4+CD8−thymocytes to self-antigen recognition, which affects the quantity of the Treg cells generated and broadens the repertoire of peripheral Tconv cells. T-cell repertoire alteration after deletion of CTLA-4 results from changes in TCR Vα and Jα segment selection as well as CDR3α composition in Tconv and Treg cells. CTLA-4, therefore, regulates the early development of self-reactive T cells in the thymus and plays a key role in central tolerance.
Resource diversity and landscape-level homogeneity drive native bee foraging
Authors: Jha Shalene , Kremen Claire
Published: December 2012

Given widespread declines in pollinator communities and increasing global reliance on pollinator-dependent crops, there is an acute need to develop a mechanistic understanding of native pollinator population and foraging biology. Using a population genetics approach, we determine the impact of habitat and floral resource distributions on nesting and foraging patterns of a critical native pollinator,
Bombus vosnesenskii
. Our findings demonstrate that native bee foraging is far more plastic and extensive than previously believed and does not follow a simple optimal foraging strategy. Rather, bumble bees forage further in pursuit of species-rich floral patches and in landscapes where patch-to-patch variation in floral resources is less, regardless of habitat composition. Thus, our results reveal extreme foraging plasticity and demonstrate that floral diversity, not density, drives bee foraging distance. Furthermore, we find a negative impact of paved habitat and a positive impact of natural woodland on bumble bee nesting densities. Overall, this study reveals that natural and human-altered landscapes can be managed for increased native bee nesting and extended foraging, dually enhancing biodiversity and the spatial extent of pollination services.
Tumor cell-derived placental growth factor sensitizes antiangiogenic and antitumor effects of anti-VEGF drugs
Authors: Hedlund Eva-Maria Eleonora , Yang Xiaojuan , Zhang Yin , Yang Yunlong , Shibuya Masabumi , Zhong Weide , Sun Baocun , Liu Yizhi , Hosaka Kayoko , Cao Yihai
Published: December 2012

The role of placental growth factor (PlGF) in modulation of tumor angiogenesis and tumor growth remains an enigma. Furthermore, anti-PlGF therapy in tumor angiogenesis and tumor growth remains controversial in preclinical tumor models. Here we show that in both human and mouse tumors, PlGF induced the formation of dilated and normalized vascular networks that were hypersensitive to anti-VEGF and anti–VEGFR-2 therapy, leading to dormancy of a substantial number of avascular tumors. Loss-of-function using
plgf
shRNA in a human choriocarcinoma significantly accelerated tumor growth rates and acquired resistance to anti-VEGF drugs, whereas gain-of-function of PlGF in a mouse tumor increased anti-VEGF sensitivity. Further, we show that VEGFR-2 and VEGFR-1 blocking antibodies displayed opposing effects on tumor angiogenesis. VEGFR-1 blockade and genetic deletion of the tyrosine kinase domain of VEGFR-1 resulted in enhanced tumor angiogenesis. These findings demonstrate that tumor-derived PlGF negatively modulates tumor angiogenesis and tumor growth and may potentially serve as a predictive marker of anti-VEGF cancer therapy.
Water, plants, and early human habitats in eastern Africa
Authors: Magill Clayton R. , Ashley Gail M. , Freeman Katherine H.
Published: December 2012

Water and its influence on plants likely exerted strong adaptive pressures in human evolution. Understanding relationships among water, plants, and early humans is limited both by incomplete terrestrial records of environmental change and by indirect proxy data for water availability. Here we present a continuous record of stable hydrogen-isotope compositions (expressed as
δ
D values) for lipid biomarkers preserved in lake sediments from an early Pleistocene archaeological site in eastern Africa—Olduvai Gorge. We convert sedimentary leaf- and algal-lipid δD values into estimates for ancient source-water δD values by accounting for biochemical, physiological, and environmental influences on isotopic fractionation via published water–lipid enrichment factors for living plants, algae, and recent sediments. Reconstructed precipitation and lake-water δD values, respectively, are consistent with modern isotopic hydrology and reveal that dramatic fluctuations in water availability accompanied ecosystem changes. Drier conditions, indicated by less negative δD values, occur in association with stable carbon-isotopic evidence for open, C
4
-dominated grassland ecosystems. Wetter conditions, indicated by lower δD values, are associated with expanded woody cover across the ancient landscape. Estimates for ancient precipitation amounts, based on reconstructed precipitation δD values, range between approximately 250 and 700 mm·y
−1
and are consistent with modern precipitation data for eastern Africa. We conclude that freshwater availability exerted a substantial influence on eastern African ecosystems and, by extension, was central to early human proliferation during periods of rapid climate change.
Trace element diffusivities in bone rule out simple diffusive uptake during fossilization but explain in vivo uptake and release
Authors: Kohn Matthew J. , Moses Randolph J.
Published: December 2012

Diffusion rates of numerous trace elements in bone at 20 °C were determined using laser-ablation inductively coupled plasma mass spectrometry analysis of experimentally induced diffusion profiles. Diffusivities are about 1 order of magnitude slower than current semiquantitative geochemical views and about 1.5 orders of magnitude faster than indirect radiotracer estimates. Intrabone volume diffusion is too slow and too similar among many elements to explain trace element profiles in young fossils and archeological materials. Diffusivity differences among elements do, however, explain disparate biokinetic washout of Sr vs. Ba and of light vs. heavy rare earth elements (REEs). These results improve the understanding of the physical principles underlying biokinetic models and rates and mechanisms of trace element alteration of phosphatic tissues in paleontological, archeological, and crystal-chemical contexts. Recrystallization and transport limitations in soils explain trace element profiles in young fossils better than intrabone volume diffusion alone and imply that diffusion of REE and other trivalent cations is likely controlled by a common charge–compensating species rather than ionic radii or partition coefficients.
Growth of
Carnobacterium
spp. from permafrost under low pressure, temperature, and anoxic atmosphere has implications for Earth microbes on Mars
Authors: Nicholson Wayne L. , Krivushin Kirill , Gilichinsky David , Schuerger Andrew C.
Published: December 2012

The ability of terrestrial microorganisms to grow in the near-surface environment of Mars is of importance to the search for life and protection of that planet from forward contamination by human and robotic exploration. Because most water on present-day Mars is frozen in the regolith, permafrosts are considered to be terrestrial analogs of the martian subsurface environment. Six bacterial isolates were obtained from a permafrost borehole in northeastern Siberia capable of growth under conditions of low temperature (0 °C), low pressure (7 mbar), and a CO
2
-enriched anoxic atmosphere. By 16S ribosomal DNA analysis, all six permafrost isolates were identified as species of the genus
Carnobacterium
, most closely related to
C. inhibens
(five isolates) and
C. viridans
(one isolate). Quantitative growth assays demonstrated that the six permafrost isolates, as well as nine type species of
Carnobacterium
(
C. alterfunditum
,
C. divergens
,
C. funditum
,
C. gallinarum
,
C. inhibens
,
C. maltaromaticum
,
C. mobile
,
C. pleistocenium
, and
C. viridans
) were all capable of growth under cold, low-pressure, anoxic conditions, thus extending the low-pressure extreme at which life can function.
Marked changes in electron transport through the blue copper protein azurin in the solid state upon deuteration
Authors: Amdursky Nadav , Pecht Israel , Sheves Mordechai , Cahen David
Published: December 2012

Measuring solid-state electron transport (ETp) across proteins allows studying electron transfer (ET) mechanism(s), while minimizing solvation effects on the process. ETp is, however, sensitive to any static (conformational) or dynamic (vibrational) changes in the protein. Our macroscopic measurements allow extending ETp studies to low temperatures, with the concomitant resolution of lower current densities, because of the larger electrode contact areas. Thus, earlier we reported temperature-independent ETp via the copper protein azurin (Az), from 80 K until denaturation, whereas for apo-Az ETp was temperature dependent above 180 K. Deuteration (H/D substitution) may provide mechanistic information on the question of whether the ETp involves H-bonds in the solid state. Here we report results of kinetic deuterium isotope effect (KIE) measurements on ETp through holo-Az as a function of temperature (30–340 K). Strikingly, deuteration changed ETp from temperature independent to temperature dependent above 180 K. This H/D effect is expressed in KIE values between 1.8 (340 K) and 9.1 (≤180 K). These values are remarkable in light of the previously reported inverse KIE on ET in Az in solution. We ascribe the difference between our KIE results and those observed in solution to the dominance of solvent effects in the latter (larger thermal expansion in H2O than in D2O), whereas in our case the KIE is primarily due to intramolecular changes, mainly in the low-frequency structural modes of the protein caused by H/D exchange. The observed high KIE values are consistent with a transport mechanism that involves through-H-bonds of the β-sheet structure of Az, likely also those in the Cu coordination sphere.
ATP hydrolysis by a domain related to translation factor GTPases drives polymerization of a static bacterial morphogenetic protein
Authors: Castaing Jean-Philippe , Nagy Attila , Anantharaman Vivek , Aravind L. , Ramamurthi Kumaran S.
Published: December 2012

The assembly of static supramolecular structures is a culminating event of developmental programs. One such structure, the proteinaceous shell (called the coat) that surrounds spores of the bacterium
Bacillus subtilis
, is composed of about 70 different proteins and represents one of the most durable biological structures known. The coat is built atop a basement layer that contains an ATPase (SpoIVA) that forms a platform required for coat assembly. Here, we show that SpoIVA belongs to the translation factors class of P-loop GTPases and has evolutionarily lost the ability to bind GTP; instead, it uses ATP hydrolysis to drive its self-assembly into static filaments. We demonstrate that ATP hydrolysis is required by every subunit for incorporation into the growing polymer by inducing a conformational change that drives polymerization of a nucleotide-free filament. SpoIVA therefore differs from other self-organizing polymers (dynamic cytoskeletal structures and static intermediate filaments) in that it uses ATP hydrolysis to self-assemble, not disassemble, into a static polymer. We further show that polymerization requires a critical concentration that we propose is only achieved once SpoIVA is recruited to the surface of the developing spore, thereby ensuring that SpoIVA polymerization only occurs at the correct subcellular location during spore morphogenesis.
Proteome-wide protein interaction measurements of bacterial proteins of unknown function
Authors: Meier Matthias , Sit Rene V. , Quake Stephen R.
Published: December 2012

Despite the enormous proliferation of bacterial genome data, surprisingly persistent collections of bacterial proteins have resisted functional annotation. In a typical genome, roughly 30% of genes have no assigned function. Many of these proteins are conserved across a large number of bacterial genomes. To assign a putative function to these conserved proteins of unknown function, we created a physical interaction map by measuring biophysical interaction of these proteins. Binary protein-–protein interactions in the model organism
Streptococcus pneumoniae
(TIGR4) are measured with a microfluidic high-throughput assay technology. In some cases, informatic analysis was used to restrict the space of potential binding partners. In other cases, we performed in vitro proteome-wide interaction screens. We were able to assign putative functions to 50 conserved proteins of unknown function that we studied with this approach.
Reverse-engineering the genetic circuitry of a cancer cell with predicted intervention in chronic lymphocytic leukemia
Authors: Vallat Laurent , Kemper Corey A. , Jung Nicolas , Maumy-Bertrand Myriam , Bertrand Frédéric , Meyer Nicolas , Pocheville Arnaud , Fisher John W. , Gribben John G. , Bahram Seiamak
Published: December 2012

Cellular behavior is sustained by genetic programs that are progressively disrupted in pathological conditions—notably, cancer. High-throughput gene expression profiling has been used to infer statistical models describing these cellular programs, and development is now needed to guide orientated modulation of these systems. Here we develop a regression-based model to reverse-engineer a temporal genetic program, based on relevant patterns of gene expression after cell stimulation. This method integrates the temporal dimension of biological rewiring of genetic programs and enables the prediction of the effect of targeted gene disruption at the system level. We tested the performance accuracy of this model on synthetic data before reverse-engineering the response of primary cancer cells to a proliferative (protumorigenic) stimulation in a multistate leukemia biological model (i.e., chronic lymphocytic leukemia). To validate the ability of our method to predict the effects of gene modulation on the global program, we performed an intervention experiment on a targeted gene. Comparison of the predicted and observed gene expression changes demonstrates the possibility of predicting the effects of a perturbation in a gene regulatory network, a first step toward an orientated intervention in a cancer cell genetic program.
Electronic resonance with anticorrelated pigment vibrations drives photosynthetic energy transfer outside the adiabatic framework
Authors: Tiwari Vivek , Peters William K. , Jonas David M.
Published: December 2012

The delocalized, anticorrelated component of pigment vibrations can drive nonadiabatic electronic energy transfer in photosynthetic light-harvesting antennas. In femtosecond experiments, this energy transfer mechanism leads to excitation of delocalized, anticorrelated vibrational wavepackets on the ground electronic state that exhibit not only 2D spectroscopic signatures attributed to electronic coherence and oscillatory quantum energy transport but also a cross-peak asymmetry not previously explained by theory. A number of antennas have electronic energy gaps matching a pigment vibrational frequency with a small vibrational coordinate change on electronic excitation. Such photosynthetic energy transfer steps resemble molecular internal conversion through a nested intermolecular funnel.
Deletion of
Mthfd1l
causes embryonic lethality and neural tube and craniofacial defects in mice
Authors: Momb Jessica , Lewandowski Jordan P. , Bryant Joshua D. , Fitch Rebecca , Surman Deborah R. , Vokes Steven A. , Appling Dean R.
Published: December 2012

Maternal supplementation with folic acid is known to reduce the incidence of neural tube defects (NTDs) by as much as 70%. Despite the strong clinical link between folate and NTDs, the biochemical mechanisms through which folic acid acts during neural tube development remain undefined. The
Mthfd1l
gene encodes a mitochondrial monofunctional 10-formyl-tetrahydrofolate synthetase, termed MTHFD1L. This gene is expressed in adults and at all stages of mammalian embryogenesis with localized regions of higher expression along the neural tube, developing brain, craniofacial structures, limb buds, and tail bud. In both embryos and adults, MTHFD1L catalyzes the last step in the flow of one-carbon units from mitochondria to cytoplasm, producing formate from 10-formyl-THF. To investigate the role of mitochondrial formate production during embryonic development, we have analyzed
Mthfd1l
knockout mice. All embryos lacking
Mthfd1l
exhibit aberrant neural tube closure including craniorachischisis and exencephaly and/or a wavy neural tube. This fully penetrant folate-pathway mouse model does not require feeding a folate-deficient diet to cause this phenotype. Maternal supplementation with sodium formate decreases the incidence of NTDs and partially rescues the growth defect in embryos lacking
Mthfd1l
. These results reveal the critical role of mitochondrially derived formate in mammalian development, providing a mechanistic link between folic acid and NTDs. In light of previous studies linking a common splice variant in the human
MTHFD1L
gene with increased risk for NTDs, this mouse model provides a powerful system to help elucidate the specific metabolic mechanisms that underlie folate-associated birth defects, including NTDs.