bluuebunny/crossref_metadata_2025 huggingface dataset:
Robust control approach to force estimation in a constant position optical tweezers
Authors: Aggarwal Tanuj , Sehgal Hullas , Salapaka Murti
Published: November 2011

Feedback enhanced optical tweezers with position regulation capability enable detection and estimation of forces in the pico-Newton regime. In this article we delineate the fundamental limitations and challenges of existing approaches for regulating position and force estimation in an optical tweezer. A modern control systems approach is shown to improve the bandwidth of force estimation by three to four times which is corroborated experimentally.
The effect of a mechanical force on quantum reaction rate: Quantum Bell formula
Authors: Makarov Dmitrii E.
Published: November 2011

The purpose of this note is to derive a quantum-mechanical analog of Bell's formula, which describes the sensitivity of a chemical reaction to a mechanical pulling force. According to this formula, the reaction rate depends exponentially on the force f, i.e., k( f ) ∼ exp( f / fc), where the force scale fc is estimated as the thermal energy kBT divided by a distance a between the reactant and transition states along the pulling coordinate. Here I use instanton theory to show that, at low temperatures where quantum tunneling is dominant, this force scale becomes fc ∼ ℏω/a (in the limit where frictional damping is absent) or fc ∼ ℏτ−1/a (in the strong damping limit). Here ω is a characteristic vibration frequency along the pulling coordinate and τ is a characteristic relaxation time in the reactant state. That is, unlike the classical case where fc is unaffected by dissipation, this force scale becomes friction dependent in the quantum limit. I further derive higher-order corrections in the force dependence of the rate, describe generalizations to many degrees of freedom, and discuss connection to other quantum rate theories.
Micro and nano analysis of 0.2 Ω mm Ti/Al/Ni/Au ohmic contact to AlGaN/GaN
Authors: Fontserè A. , Pérez-Tomás A. , Placidi M. , Llobet J. , Baron N. , Chenot S. , Cordier Y. , Moreno J. C. , Gammon P. M. , Jennings M. R. , Porti M. , Bayerl A. , Lanza M. , Nafría M.
Published: November 2011

As GaN technology continues to gain popularity, it is necessary to control the ohmic contact properties and to improve device consistency across the whole wafer. In this paper, we use a range of submicron characterization tools to understand the conduction mechanisms through the AlGaN/GaN ohmic contact. Our results suggest that there is a direct path for electron flow between the two dimensional electron gas and the contact pad. The estimated area of these highly conductive pillars is around 5% of the total contact area.
Molecular simulation of interaction between passivated gold nanoparticles in supercritical CO2
Authors: Sun Ling , Yang Xiaoning , Wu Bin , Tang Lunjiang
Published: November 2011

Molecular dynamics simulations have been performed to study the potential of mean force (PMF) between passivated gold nanoparticles (NPs) in supercritical CO2 (scCO2). The nanoparticle model consists of a 140 atom gold nanocore and a surface self-assembled monolayer, in which two kinds of fluorinated alkanethiols were considered. The molecular origin of the thermodynamics interaction and the solvation effect has been comprehensively studied. The simulation results demonstrate that increasing the solvent density and ligand length can enhance the repulsive feature of the free energy between the passivated Au nanoparticles in scCO2, which is in good agreement with previous experimental results. The interaction forces between the two passivated NPs have been decomposed to reveal various contributions to the free energy. It was revealed that the interaction between capping ligands and the interaction between the capping ligands and scCO2 solvent molecules cooperatively determine the total PMF. A thermodynamic entropy-energy analysis for each PMF contribution was used to explain the density dependence of PMF in scCO2 fluid. Our simulation study is expected to provide a novel microscopic understanding of the effect of scCO2 solvent on the interaction between passivated Au nanoparticles, which is helpful to the dispersion and preparation of functional metal nanoparticles in supercritical fluids.
Binary systems from quantum cluster equilibrium theory
Authors: Brüssel Marc , Perlt Eva , Lehmann Sebastian B. C. , von Domaros Michael , Kirchner Barbara
Published: November 2011

An extension of the quantum cluster equilibrium theory to treat binary mixtures is introduced in this work. The necessary equations are derived and a possible implementation is presented. In addition an alternative sampling procedure using widely available experimental data for the quantum cluster equilibrium approach is suggested and tested. An illustrative example, namely, the binary mixture of water and dimethyl sulfoxide, is given to demonstrate the new approach. A basic cluster set is introduced containing the relevant cluster motifs. The populations computed by the quantum cluster equilibrium approach are compared to the experimental data. Furthermore, the excess Gibbs free energy is computed and compared to experiments as well.
Analysis of the torsional spectrum of monodeuterated methanol CH2DOH
Authors: El Hilali A. , Coudert L. H. , Konov I. , Klee S.
Published: November 2011

An analysis of the torsional spectrum of monodeuterated methanol CH2DOH is presented. Twenty nine torsional subbands have been assigned in the 20–800 cm−1 region. The newly assigned subbands and those already available in the literature were analyzed with a theoretical approach accounting for internal rotation of an asymmetrical CH2D methyl group. Seventy six subband centers were reproduced with an rms value of 0.09 cm−1. Spectroscopic parameters corresponding to the generalized inertia tensor and to the hindering potential were determined as well as rotation-torsion distortion constants.
Transport and optical properties of the gapless Heusler compound PtYSb
Authors: Ouardi Siham , Fecher Gerhard H. , Felser Claudia , Hamrle Jaroslav , Postava Kamil , Pištora Jaromír
Published: November 2011

This work presents a systematic study on the optical and transport properties of the Heusler compound PtYSb. The optical properties were investigated in a wide spectral range from 10 meV to 6.5 eV and compared to ab-initio calculations. For photon energies below 2.5 eV, the optical absorption increases linearly with photon energy. This is related with the conical shape of the electronic structure in the vicinity of the Fermi energy. The optical spectra reveal a maximum band gap of about 60 meV. Furthermore, the temperature dependence of thermal conductivity, electrical resistivity, Seebeck coefficient and Hall mobility were investigated. PtYSb exhibits very good thermoelectric properties with a high figure of merit ZT of 0.2 and a Hall mobility μh of 300 cm2/Vs at 350 K, which is the highest value obtained for Heusler compounds up to now. The carrier concentration ranges from 5 × 1018 at low temperature to 1019 cm−3 at 400 K.
Atomic-scale determination of band offsets at the Gd2O3/GaAs (100) hetero-interface using scanning tunneling spectroscopy
Authors: Chiu Y. P. , Huang B. C. , Shih M. C. , Shen J. Y. , Chang P. , Chang C. S. , Huang M. L. , Tsai M.-H. , Hong M. , Kwo J.
Published: November 2011

Direct measurements of band profile and band offsets across the Gd2O3/GaAs(100) hetero-interface have been performed using cross-sectional scanning tunneling microscopy and spectroscopy. The spatial variation of the local density of states with atomic precision revealed the interfacial band alignment in this model high-κ/III-V system. In conjunction with the theoretical modeling, the band offsets for both conduction and valence states are identified, revealing critical information about the electrostatic potential landscape of the GaAs semiconductor transistor with a Gd2O3 gate dielectric.
Graphene arch gate SiO2 shell silicon nanowire core field effect transistors
Authors: Jin J. E. , Lee J. H. , Hwang D. H. , Kim D. W. , Kim M. J. , Son K. S. , Whang D. , Hwang S. W.
Published: November 2011

We report the realization of graphene arch gate silicon nanowire field effect transistors with SiO2 shell serving as a gate insulator. The arch coverage of the SiO2 shell was achieved by the flexible graphene layers complying the top of the shell. The wrapping angle was defined by the relative strength of the van der Waals forces on the shell and the substrate. The leakage current of the graphene gate was only 55 fA, while the maximum on-off ratio of 16.7 was obtained. The effective mobility and quantum capacitance of the graphene layers were also obtained from the electronic transport data.
High-frequency nanotube mechanical resonators
Authors: Chaste J. , Sledzinska M. , Zdrojek M. , Moser J. , Bachtold A.
Published: November 2011

We report on a simple method to fabricate high-frequency nanotube mechanical resonators reproducibly. We measure resonance frequencies as high as 4.2 GHz for the fundamental eigenmode and 11 GHz for higher order eigenmodes. The high-frequency resonances are achieved using short suspended nanotubes and by introducing tensile stress in the nanotube. These devices allow us to determine the coefficient of the thermal expansion of an individual nanotube, which is negative and is about -0.7·10-51/K at room temperature. High-frequency resonators made of nanotubes hold promise for mass sensing and experiments in the quantum limit.
Low density carbon nanotube forest as an index-matched and near perfect absorption coating
Authors: Shi Haofei , Ok Jong G. , Won Baac Hyoung , Jay Guo L.
Published: November 2011

We demonstrate broadband, near perfect absorption with a conformal coating of a multi-walled carbon nanotube (CNT) forest on an arbitrarily shaped surface. The complex refractive index of such a CNT forest is retrieved from the measured transmission and reflection spectra using Kramers-Kronig constrained variational analysis, which gives a typical value of neff = 1.04 + 0.01i at visible wavelengths. Therefore, when used as a conformal coating on an object, a thick layer of the CNT forest can provide an excellent impedance match to air and near perfect absorption, preventing any detectable light reflection and scattering from the object.
Optical resonances in tubular microcavities with subwavelength wall thicknesses
Authors: Zhan Tianrong , Xu Chun , Zhao Fangyuan , Xiong Zhiqiang , Hu Xinhua , Huang Gaoshan , Mei Yongfeng , Zi Jian
Published: November 2011

Based on the Mie scattering theory, we study optical resonances with whispering gallery modes (WGMs) in tubular microcavities. Rigorous formulas are present to obtain resonant wavelengths and Q factors for the WGM resonances. It is found that the Q factors of microtubes can be dramatically increased by increasing the dielectric constants in tube walls. For common SiO/SiO2 based microtubes, Q factors can be improved by one order when the microtubes are coated with thin high-index HfO2 layers (n = 1.95, thickness = 10 nm). The results could be useful for designing better optical devices based on tubular microcavities.
Surface-Enhanced Raman Scattering of the Bariandite Oxide Layer on a Vanadium Dioxide Crystal
Authors: Butler Ian S. , Beattie James K.
Published: November 2011

Variable-temperature (25–100°C) Raman spectra of a crystal of commercial VO2 have revealed surface-enhanced Raman scattering (SERS) of the V=O stretching mode of the bariandite-like vanadium oxide species, V10O24·9H2O, that is formed on the surface of the crystal. Upon passing through the semiconductor-to-metal phase transition of VO2 at 68°C, there is an approximately three to five-fold increase in Raman intensity of the V=O stretching mode. This effect is reversible with hysteresis upon decreasing the temperature. The temperature dependence of the Raman spectra at temperatures below the transition suggest that even the semiconductor phase has some SERS effect.
Cryptic grey-bellied dunnart (Sminthopsis griseoventer) discovered in South Australia: genetic, morphological and subfossil analyses show the value of collecting voucher material
Authors: Kemper Catherine M. , Cooper Steven J. B. , Medlin Graham C. , Adams Mark , Stemmer David , Saint Kathleen M. , McDowell Matthew C. , Austin Jeremy J.
Published: November 2011

The assumption that almost all mammal species are known to science has led to a recent trend away from collecting voucher specimens/tissues during field studies. Here we present a case study of a recently discovered cryptic marsupial (Sminthopsis griseoventer) in South Australia (SA) and show how such collections can contribute to rigorous biodiversity and biogeographic assessments. Morphological and genetic (allozyme and mitochondrial control region (CR) sequence data) analyses, including ancient DNA analyses of type material, were applied to 188 voucher specimens and 94 non-vouchered tissues of Sminthopsis held at the SA Museum. These data were used to confirm the presence of S. griseoventer in SA, validate means of identifying it morphologically and describe recent and pre-European distributions. Pelage differences between S. griseoventer and S. dolichura enabled their identification, but external measurements overlapped considerably. Subfossil S. griseoventer were identified from seven deposits and confirmed that in the past the species was more widespread in SA. CR divergences (>1.8%) among Western Australian and SA S. griseoventer suggested its long-term presence in SA. Discrepancies between the mitochondrial and allozyme affinities of S. aitkeni and S. griseoventer, coupled with the lack of obvious morphological differences, indicate that a taxonomic reappraisal of these species is warranted. The study strongly demonstrates an ongoing need for the routine collection of mammal voucher material in biological and environmental impact surveys.
Stardust in meteorites
Authors: Davis Andrew M.
Published: November 2011

Primitive meteorites, interplanetary dust particles, and comets contain dust grains that formed around stars that lived their lives before the solar system formed. These remarkable objects have been intensively studied since their discovery a little over twenty years ago and they provide samples of other stars that can be studied in the laboratory in exquisite detail with modern analytical tools. The properties of stardust grains are used to constrain models of nucleosynthesis in red giant stars and supernovae, the dominant sources of dust grains that are recycled into the interstellar medium by stars.
The inflammasome promotes adverse cardiac remodeling following acute myocardial infarction in the mouse
Authors: Mezzaroma Eleonora , Toldo Stefano , Farkas Daniela , Seropian Ignacio M. , Van Tassell Benjamin W. , Salloum Fadi N. , Kannan Harsha R. , Menna Angela C. , Voelkel Norbert F. , Abbate Antonio
Published: November 2011

Acute myocardial infarction (AMI) initiates an intense inflammatory response that promotes cardiac dysfunction, cell death, and ventricular remodeling. The molecular events underlying this inflammatory response, however, are incompletely understood. In experimental models of sterile inflammation, ATP released from dying cells triggers, through activation of the purinergic P2X7 receptor, the formation of the inflammasome, a multiprotein complex necessary for caspase-1 activation and amplification of the inflammatory response. Here we describe the presence of the inflammasome in the heart in an experimental mouse model of AMI as evidenced by increased caspase-1 activity and cytoplasmic aggregates of the three components of the inflammasome—apoptosis speck-like protein containing a caspase-recruitment domain (ASC), cryopyrin, and caspase-1, localized to the granulation tissue and cardiomyocytes bordering the infarct. Cultured adult murine cardiomyocytes also showed the inducible formation of the inflammasome associated with increased cell death. P2X7 and cryopyrin inhibition (using silencing RNA or a pharmacologic inhibitor) prevented the formation of the inflammasome and limited infarct size and cardiac enlargement after AMI. The formation of the inflammasome in the mouse heart during AMI causes additional loss of functional myocardium, leading to heart failure. Modulation of the inflammasome may therefore represent a unique therapeutic strategy to limit cell death and prevent heart failure after AMI.
Prostagladin D
2
is a mast cell-derived antiangiogenic factor in lung carcinoma
Authors: Murata Takahisa , Aritake Kosuke , Matsumoto Shigeko , Kamauchi Shinya , Nakagawa Takayuki , Hori Masatoshi , Momotani Eiichi , Urade Yoshihiro , Ozaki Hiroshi
Published: November 2011

It is well established that prostaglandins (PGs) are involved in tumor angiogenesis and growth, yet the role of prostaglandin D
2
(PGD
2
) remains virtually unknown. Here, we show that host hematopoietic PGD
2
synthase (H-PGDS) deficiency enhances Lewis lung carcinoma (LLC) progression, accompanied by increased vascular leakage, angiogenesis, and monocyte/mast cell infiltration. This deficiency can be rescued by hematopoietic reconstitution with bone marrow from H-PGDS–naive (WT) mice. In tumors on WT mice, c-kit
+
mast cells highly express H-PGDS. Host H-PGDS deficiency markedly up-regulated the expression of proangiogenic factors, including TNF-α in the tumor. In mast cell-null Kit
W-sh/W-sh
mice, adoptive transfer of H-PGDS–deficient mast cells causes stronger acceleration in tumor angiogenesis and growth than in WT mast cells. In response to LLC growth, H-PGDS–deficient mast cells produce TNF-α excessively. This response is suppressed by the administration of a synthetic PGD
2
receptor agonist or a degradation product of PGD
2
, 15-deoxy-Δ
12,14
-PGJ
2
. Additional TNF-α deficiency partially counteracts the tumorigenic properties seen in H-PGDS–deficient mast cells. These observations identify PGD
2
as a mast cell-derived antiangiogenic factor in expanding solid tumors. Mast cell-derived PGD
2
governs the tumor microenvironment by restricting excessive responses to vascular permeability and TNF-α production.
Promoter regulation by distinct mechanisms of functional interplay between lysine acetylase Rtt109 and histone chaperone Asf1
Authors: Lin Ling-ju , Schultz Michael C.
Published: November 2011

The promoter activity of yeast genes can depend on lysine 56 (K56) acetylation of histone H3. This modification of H3 is performed by lysine acetylase Rtt109 acting in concert with histone chaperone Asf1. We have examined the contributions of Rtt109, Asf1, and H3 K56 acetylation to nutrient regulation of a well-studied metabolic gene,
ARG1
. As expected, Rtt109, Asf1, and H3 K56 acetylation are required for maximal transcription of
ARG1
under inducing conditions. However, Rtt109 and Asf1 also inhibit
ARG1
under repressing conditions. This inhibition requires Asf1 binding to H3-H4 and Rtt109 KAT activity, but not tail acetylation of H3-H4 or K56 acetylation of H3. These observations suggest the existence of a unique mechanism of transcriptional regulation by Rtt109. Indeed, chromatin immunoprecipitation and genetic interaction studies support a model in which promoter-targeted Rtt109 represses
ARG1
by silencing a pathway of transcriptional activation that depends on
ASF1
. Collectively, our results show that
ARG1
transcription intensity at its induced and repressed set points is controlled by different mechanisms of functional interplay between Rtt109 and Asf1.
Activated protein C promotes protease-activated receptor-1 cytoprotective signaling through β-arrestin and dishevelled-2 scaffolds
Authors: Soh Unice J. K. , Trejo JoAnn
Published: November 2011

Protease-activated receptor-1 (PAR1) is a guanine nucleotide-binding (G) protein-coupled receptor that elicits cellular responses to coagulant and anticoagulant proteases. Activation of PAR1 by the coagulant protease thrombin results in Ras homolog gene family member A (RhoA) activation, disassembly of adherens junctions, and disruption of the endothelial barrier. In contrast, activation of PAR1 with the anticoagulant protease activated protein C (APC) results in activation of Ras-related C3 botulinum toxin substrate 1 (Rac1) and endothelial barrier protection. We previously showed that APC cytoprotective signaling requires the compartmentalization of PAR1 in caveolar microdomains. However, the mechanism by which APC-activated PAR1 promotes cytoprotective signaling in human endothelial cells remains poorly understood. Here we show that APC-activated PAR1 cytoprotective signaling is mediated by β-arrestin recruitment and activation of the dishevelled-2 (Dvl-2) scaffold and not by G protein α inhibiting activity polypeptide 2 (Gα
i
) signaling. In human endothelial cells, PAR1 and β-arrestins form a preassembled complex and cosegregate in caveolin-1–enriched fractions. Remarkably, we found that depletion of β-arrestin expression by RNA interference resulted in the loss of APC-induced Rac1 activation but not of thrombin-stimulated RhoA signaling. APC also failed to protect against thrombin-induced endothelial barrier permeability in cells deficient in β-arrestin expression. We further demonstrate that APC activation of PAR1 results in β-arrestin–dependent recruitment of Dvl-2, which is critical for Rac1 signaling and endothelial barrier protection but not for thrombin-induced RhoA signaling. Our findings identify a role for β-arrestin and Dvl-2 scaffolds in APC-activated PAR1 cytoprotective signaling in human endothelial cells.
Benefits of wildlife consumption to child nutrition in a biodiversity hotspot
Authors: Golden Christopher D. , Fernald Lia C. H. , Brashares Justin S. , Rasolofoniaina B. J. Rodolph , Kremen Claire
Published: November 2011

Terrestrial wildlife is the primary source of meat for hundreds of millions of people throughout the developing world. Despite widespread human reliance on wildlife for food, the impact of wildlife depletion on human health remains poorly understood. Here we studied a prospective longitudinal cohort of 77 preadolescent children (under 12 y of age) in rural northeastern Madagascar and show that consuming more wildlife was associated with significantly higher hemoglobin concentrations. Our empirical models demonstrate that removing access to wildlife would induce a 29% increase in the numbers of children suffering from anemia and a tripling of anemia cases among children in the poorest households. The well-known progression from anemia to future disease demonstrates the powerful and far-reaching effects of lost wildlife access on a variety of human health outcomes, including cognitive, motor, and physical deficits. Loss of access to wildlife could arise either from the diligent enforcement of existing conservation policy or from unbridled unsustainable harvest, leading to depletion. Conservation enforcement would enact a more rapid restriction of resources, but self-depletion would potentially lead, albeit more slowly, both to irrevocable local wildlife extinctions and loss of the harvested resource. Our research quantifies costs of reduced access to wildlife for a rural community in Madagascar and illuminates pathways that may broadly link reduced natural resource access to declines in childhood health.
Displacement of the canonical single-stranded DNA-binding protein in the Thermoproteales
Authors: Paytubi Sonia , McMahon Stephen A. , Graham Shirley , Liu Huanting , Botting Catherine H. , Makarova Kira S. , Koonin Eugene V. , Naismith James H. , White Malcolm F.
Published: November 2011

ssDNA-binding proteins (SSBs) based on the oligonucleotide-binding fold are considered ubiquitous in nature and play a central role in many DNA transactions including replication, recombination, and repair. We demonstrate that the Thermoproteales, a clade of hyperthermophilic Crenarchaea, lack a canonical SSB. Instead, they encode a distinct ssDNA-binding protein that we term “ThermoDBP,” exemplified by the protein Ttx1576 from
Thermoproteus tenax
. ThermoDBP binds specifically to ssDNA with low sequence specificity. The crystal structure of Ttx1576 reveals a unique fold and a mechanism for ssDNA binding, consisting of an extended cleft lined with hydrophobic phenylalanine residues and flanked by basic amino acids. Two ssDNA-binding domains are linked by a coiled-coil leucine zipper. ThermoDBP appears to have displaced the canonical SSB during the diversification of the Thermoproteales, a highly unusual example of the loss of a “ubiquitous” protein during evolution.
What dopamine does in the brain
Authors: Snyder Solomon H.
Published: November 2011

In the early 1970s, receptors for neurotransmitters acting via second messengers had not been identified biochemically nor were there definitive links to such messengers. The discovery by John W. Kebabian and Paul Greengard of a dopamine-sensitive adenyl cyclase, accordingly, was a giant step forward. The investigators first characterized the enzyme in sympathetic ganglia wherein dopamine-producing cells link pre- and post-synaptic neurons. Then, in the corpus striatum, the brain area enriched in dopamine, they delineated the enzyme\x{2019}s properties and showed that it was inhibited by antipsychotic drugs, leading to a large body of research on dopamine as a mediator of antipsychotic drug action and putative roles for this transmitter in the pathophysiology of schizophrenia.
Phospholipase D2 (PLD2) is a guanine nucleotide exchange factor (GEF) for the GTPase Rac2
Authors: Mahankali Madhu , Peng Hong-Juan , Henkels Karen M. , Dinauer Mary C. , Gomez-Cambronero Julian
Published: November 2011

We have discovered that the enzyme phospholipase D2 (PLD2) binds directly to the small GTPase Rac2, resulting in PLD2 functioning as a guanine nucleotide exchange factor (GEF), because it switches Rac2 from the GDP-bound to the GTP-bound states. This effect is large enough to be meaningful (∼72% decrease for GDP dissociation and 300% increase for GTP association, both with PLD2), it has a half-time of ∼7 min, is enhanced with increasing PLD2 concentrations, and compares favorably with other known GEFs, such as Vav-1. The PLD2-Rac2 protein–protein interaction is sufficient for the GEF function, because it can be demonstrated in vitro with just recombinant proteins without lipid substrates, and a catalytically inactive lipase (PLD2-K758R) has GEF activity. Apart from this function, exogenous phosphatidic acid by itself (300 pM) increases GTP binding and enhances PLD2-K758R–mediated GTP binding (by ∼34%) but not GDP dissociation. Regarding the PLD2-Rac2 protein–protein association, it involves, for PLD2, residues 263–266 within a Cdc42/Rac interactive binding region in the PH domain, as well as the PX domain, and it involves, for Rac2, residue N17 within its Switch-1 region. PLD2's GEF function is demonstrated in living cells, because silencing PLD2 results in reduced Rac2 activity, whereas PLD2-initiated Rac2 activation enhances cell adhesion, chemotaxis, and phagocytosis. There are several known GEFs, but we report that this GEF is harbored in a phospholipase. The benefit to the cell is that PLD2 brings spatially separated molecules together in a membrane environment, ready for fast intracellular signaling and cell function.
Single-molecule protein arrays enabled by scanning probe block copolymer lithography
Authors: Chai Jinan , Wong Lu Shin , Giam Louise , Mirkin Chad A.
Published: November 2011

The ability to control the placement of individual protein molecules on surfaces could enable advances in a wide range of areas, from the development of nanoscale biomolecular devices to fundamental studies in cell biology. Such control, however, remains a challenge in nanobiotechnology due to the limitations of current lithographic techniques. Herein we report an approach that combines scanning probe block copolymer lithography with site-selective immobilization strategies to create arrays of proteins down to the single-molecule level with arbitrary pattern control. Scanning probe block copolymer lithography was used to synthesize individual sub-10-nm single crystal gold nanoparticles that can act as scaffolds for the adsorption of functionalized alkylthiol monolayers, which facilitate the immobilization of specific proteins. The number of protein molecules that adsorb onto the nanoparticles is dependent upon particle size; when the particle size approaches the dimensions of a protein molecule, each particle can support a single protein. This was demonstrated with both gold nanoparticle and quantum dot labeling coupled with transmission electron microscopy imaging experiments. The immobilized proteins remain bioactive, as evidenced by enzymatic assays and antigen-antibody binding experiments. Importantly, this approach to generate single-biomolecule arrays is, in principle, applicable to many parallelized cantilever and cantilever-free scanning probe molecular printing methods.
Global food demand and the sustainable intensification of agriculture
Authors: Tilman David , Balzer Christian , Hill Jason , Befort Belinda L.
Published: November 2011

Global food demand is increasing rapidly, as are the environmental impacts of agricultural expansion. Here, we project global demand for crop production in 2050 and evaluate the environmental impacts of alternative ways that this demand might be met. We find that per capita demand for crops, when measured as caloric or protein content of all crops combined, has been a similarly increasing function of per capita real income since 1960. This relationship forecasts a 100–110% increase in global crop demand from 2005 to 2050. Quantitative assessments show that the environmental impacts of meeting this demand depend on how global agriculture expands. If current trends of greater agricultural intensification in richer nations and greater land clearing (extensification) in poorer nations were to continue, ∼1 billion ha of land would be cleared globally by 2050, with CO2-C equivalent greenhouse gas emissions reaching ∼3 Gt y−1and N use ∼250 Mt y−1by then. In contrast, if 2050 crop demand was met by moderate intensification focused on existing croplands of underyielding nations, adaptation and transfer of high-yielding technologies to these croplands, and global technological improvements, our analyses forecast land clearing of only ∼0.2 billion ha, greenhouse gas emissions of ∼1 Gt y−1, and global N use of ∼225 Mt y−1. Efficient management practices could substantially lower nitrogen use. Attainment of high yields on existing croplands of underyielding nations is of great importance if global crop demand is to be met with minimal environmental impacts.
Dopamine neurons code subjective sensory experience and uncertainty of perceptual decisions
Authors: de Lafuente Victor , Romo Ranulfo
Published: November 2011

Midbrain dopamine (DA) neurons respond to sensory stimuli associated with future rewards. When reward is delivered probabilistically, DA neurons reflect this uncertainty by increasing their firing rates in a period between the sensory cue and reward delivery time. Probability of reward, however, has been externally conveyed by visual cues, and it is not known whether DA neurons would signal uncertainty arising internally. Here we show that DA neurons code the uncertainty associated with a perceptual judgment about the presence or absence of a vibrotactile stimulus. We observed that uncertainty modulates the activity elicited by a
go
cue instructing monkey subjects to communicate their decisions. That is, the same
go
cue generates different DA responses depending on the uncertainty level of a judgment made a few seconds before the
go
instruction. Easily detected suprathreshold stimuli elicit small DA responses, indicating that future reward will not be a surprising event. In contrast, the absence of a sensory stimulus generates large DA responses associated with uncertainty: was the stimulus truly absent, or did a low-amplitude vibration go undetected? In addition, the responses of DA neurons to the stimulus itself increase with vibration amplitude, but only when monkeys correctly detect its presence. This finding suggests that DA activity is not related to actual intensity but rather to perceived intensity. Therefore, in addition to their well-known role in reward prediction, DA neurons code subjective sensory experience and uncertainty arising internally from perceptual decisions.
Hypoxia promotes isocitrate dehydrogenase-dependent carboxylation of α-ketoglutarate to citrate to support cell growth and viability
Authors: Wise David R. , Ward Patrick S. , Shay Jessica E. S. , Cross Justin R. , Gruber Joshua J. , Sachdeva Uma M. , Platt Jesse M. , DeMatteo Raymond G. , Simon M. Celeste , Thompson Craig B.
Published: November 2011

Citrate is a critical metabolite required to support both mitochondrial bioenergetics and cytosolic macromolecular synthesis. When cells proliferate under normoxic conditions, glucose provides the acetyl-CoA that condenses with oxaloacetate to support citrate production. Tricarboxylic acid (TCA) cycle anaplerosis is maintained primarily by glutamine. Here we report that some hypoxic cells are able to maintain cell proliferation despite a profound reduction in glucose-dependent citrate production. In these hypoxic cells, glutamine becomes a major source of citrate. Glutamine-derived α-ketoglutarate is reductively carboxylated by the NADPH-linked mitochondrial isocitrate dehydrogenase (IDH2) to form isocitrate, which can then be isomerized to citrate. The increased IDH2-dependent carboxylation of glutamine-derived α-ketoglutarate in hypoxia is associated with a concomitant increased synthesis of 2-hydroxyglutarate (2HG) in cells with wild-type IDH1 and IDH2. When either starved of glutamine or rendered IDH2-deficient by RNAi, hypoxic cells are unable to proliferate. The reductive carboxylation of glutamine is part of the metabolic reprogramming associated with hypoxia-inducible factor 1 (HIF1), as constitutive activation of HIF1 recapitulates the preferential reductive metabolism of glutamine-derived α-ketoglutarate even in normoxic conditions. These data support a role for glutamine carboxylation in maintaining citrate synthesis and cell growth under hypoxic conditions.
A genomic storm in critically injured humans
Authors: Xiao Wenzhong , Mindrinos Michael N. , Seok Junhee , Cuschieri Joseph , Cuenca Alex G. , Gao Hong , Hayden Douglas L. , Hennessy Laura , Moore Ernest E. , Minei Joseph P. , Bankey Paul E. , Johnson Jeffrey L. , Sperry Jason , Nathens Avery B. , Billiar Timothy R. , West Michael A. , Brownstein Bernard H. , Mason Philip H. , Baker Henry V. , Finnerty Celeste C. , Jeschke Marc G. , López M. Cecilia , Klein Matthew B. , Gamelli Richard L. , Gibran Nicole S. , Arnoldo Brett , Xu Weihong , Zhang Yuping , Calvano Steven E. , McDonald-Smith Grace P. , Schoenfeld David A. , Storey John D. , Cobb J. Perren , Warren H. Shaw , Moldawer Lyle L. , Herndon David N. , Lowry Stephen F. , Maier Ronald V. , Davis Ronald W. , Tompkins Ronald G.
Published: November 2011

Human survival from injury requires an appropriate inflammatory and immune response. We describe the circulating leukocyte transcriptome after severe trauma and burn injury, as well as in healthy subjects receiving low-dose bacterial endotoxin, and show that these severe stresses produce a global reprioritization affecting >80% of the cellular functions and pathways, a truly unexpected “genomic storm.” In severe blunt trauma, the early leukocyte genomic response is consistent with simultaneously increased expression of genes involved in the systemic inflammatory, innate immune, and compensatory antiinflammatory responses, as well as in the suppression of genes involved in adaptive immunity. Furthermore, complications like nosocomial infections and organ failure are not associated with any genomic evidence of a second hit and differ only in the magnitude and duration of this genomic reprioritization. The similarities in gene expression patterns between different injuries reveal an apparently fundamental human response to severe inflammatory stress, with genomic signatures that are surprisingly far more common than different. Based on these transcriptional data, we propose a new paradigm for the human immunological response to severe injury.
Clonal analysis reveals multiple functional defects of aged murine hematopoietic stem cells
Authors: Dykstra Brad , Olthof Sandra , Schreuder Jaring , Ritsema Martha , de Haan Gerald
Published: November 2011

Hematopoietic stem cell (HSC) populations change with aging, but the extent to which this is caused by qualitative versus quantitative alterations in HSC subtypes is unclear. Using clonal assays, in this study we show that the aging HSC compartment undergoes both quantitative and qualitative changes. We observed a variable increase of HSC pool size with age, accompanied by the accumulation of predominantly myeloid-biased HSCs that regenerate substantially fewer mature progeny than young myeloid-biased HSCs and exhibit reduced self-renewal activity as measured by long-term secondary transplantation. Old HSCs had a twofold reduction in marrow-homing efficiency and a similar decrease in functional frequency as measured using long-term transplantation assays. Similarly, old HSCs had a twofold reduced seeding efficiency and a significantly delayed proliferative response compared with young HSCs in long-term stromal cell co-cultures but were indistinguishable in suspension cultures. We show that these functional defects are characteristics of most or all old HSCs and are not indicative of a nonfunctional subset of cells that express HSC markers. Furthermore, we demonstrate that cells with functional properties of old HSCs can be generated directly from young HSCs by extended serial transplantation, which is consistent with the possibility that they arise through a process of cellular aging.
Magnetoresistance in FeCoZr–Al2O3 nanocomposite films containing ‘metal core–oxide shell’ nanogranules
Authors: Fedotova J A , Przewoznik J , Kapusta Cz , Milosavljević M , Kasiuk J V , Zukrowski J , Sikora M , Maximenko A A , Szepietowska D , Homewood K P
Published: November 2011

Temperature and magnetic field dependences of electrical conductivity are systematically studied in granular films (Fe45Co45Zr10)
x
(Al2O3)100−x
(28 ⩽ x ⩽ 64) containing crystalline metallic α-FeCo-based nanoalloy cores encapsulated in an amorphous oxide shell embedded in an amorphous Al2O3 matrix. Formation of ‘metallic core–oxide shell’ nanogranules is confirmed by transmission electron microscopy (TEM) and HRTEM. The structure of core and shell is governed with the difference in the oxidation states of Fe and Co ions investigated with EXAFS, XANES and Mössbauer spectroscopy. A considerable negative magnetoresistance (MR) effect of spin-dependent nature is observed in the whole range of x values. Its increase with decreasing temperature is correlated with the magnetic saturation of superparamagnetic metallic nanogranules. The enhanced MR effect in ‘core–shell’ granular films is related to the percolation of oxide shells and their influence through spin filtering processes. A considerable high field MR at low temperatures and the resulting deviation of MR and squared magnetization are attributed to a magnetic randomness and/or strong magnetic anisotropy of the magnetic oxide shell.
Integrating human and murine anatomical gene expression data for improved comparisons
Authors: Jiménez-Lozano Natalia , Segura Joan , Macías José Ramón , Vega Juanjo , Carazo José María
Published: November 2011

Motivation: Information concerning the gene expression pattern in four dimensions (species, genes, anatomy and developmental stage) is crucial for unraveling the roles of genes through time. There are a variety of anatomical gene expression databases, but extracting information from them can be hampered by their diversity and heterogeneity.

Results: aGEM 3.1 (anatomic Gene Expression Mapping) addresses the issues of diversity and heterogeneity of anatomical gene expression databases by integrating six mouse gene expression resources (EMAGE, GXD, GENSAT, Allen Brain Atlas data base, EUREXPRESS and BioGPS) and three human gene expression databases (HUDSEN, Human Protein Atlas and BioGPS). Furthermore, aGEM 3.1 provides new cross analysis tools to bridge these resources.

Availability and implementation: aGEM 3.1 can be queried using gene and anatomical structure. Output information is presented in a friendly format, allowing the user to display expression maps and correlation matrices for a gene or structure during development. An in-depth study of a specific developmental stage is also possible using heatmaps that relate gene expression with anatomical components. http://agem.cnb.csic.es

Contact:  natalia@cnb.csic.es

Supplementary information:  Supplementary data are available at Bioinformatics online.
Identification of context-specific gene regulatory networks with GEMULA—gene expression modeling using LAsso
Authors: Geeven Geert , van Kesteren Ronald E. , Smit August B. , de Gunst Mathisca C. M.
Published: November 2011

Motivation: Gene regulatory networks, in which edges between nodes describe interactions between transcriptional regulators and their target genes, determine the coordinated spatiotemporal expression of genes. Especially in higher organisms, context-specific combinatorial regulation by transcription factors (TFs) is believed to determine cellular states and fates. TF–target gene interactions can be studied using high-throughput techniques such as ChIP-chip or ChIP-Seq. These experiments are time and cost intensive, and further limited by, for instance, availability of high affinity TF antibodies. Hence, there is a practical need for methods that can predict TF–TF and TF–target gene interactions in silico, i.e. from gene expression and DNA sequence data alone. We propose GEMULA, a novel approach based on linear models to predict TF–gene expression associations and TF–TF interactions from experimental data. GEMULA is based on linear models, fast and considers a wide range of biologically plausible models that describe gene expression data as a function of predicted TF binding to gene promoters.

Results: We show that models inferred with GEMULA are able to explain roughly 70% of the observed variation in gene expression in the yeast heat shock response. The functional relevance of the inferred TF–TF interactions in these models are validated by different sources of independent experimental evidence. We also have applied GEMULA to an in vitro model of neuronal outgrowth. Our findings confirm existing knowledge on gene regulatory interactions underlying neuronal outgrowth, but importantly also generate new insights into the temporal dynamics of this gene regulatory network that can now be addressed experimentally.

Availability: The GEMULAR-package is available from http://www.few.vu.nl/~degunst/gemula_1.0.tar.gz.

Contact:  g.geeven@hubrecht.eu

Supplementary information:  Supplementary data are available at Bioinformatics online.
Advice under uncertainty in the marine system
Authors: Dankel Dorothy J. , Aps Robert , Padda Gurpreet , Röckmann Christine , van der Sluijs Jeroen P. , Wilson Douglas C. , Degnbol Poul
Published: November 2011

Dankel, D. J., Aps, R., Padda, G., Röckmann, C., van der Sluijs, J. P., Wilson, D. C., and Degnbol, P. 2012. Advice under uncertainty in the marine system. – ICES Journal of Marine Science, 69: 3–7. There is some uncertainty in the fisheries science–policy interface. Although progress has been made towards more transparency and participation in fisheries science in ICES Areas, routine use of state-of-the-art quantitative and qualitative tools to address uncertainty systematically is still lacking. Fisheries science that gives advice to policy-making is plagued by uncertainties; the stakes of the policies are high and value-laden and need therefore to be treated as an example of “post-normal science” (PNS). To achieve robust governance, understanding of the characteristics and implications of the scientific uncertainties for management strategies need to come to the centre of the table. This can be achieved using state-of-the-art tools such as pedigree matrices and uncertainty matrices, as developed by PNS scholars and used in similar science–policy arenas on other complex issues. An explicit extension of the peer community within maritime systems will be required to put these new tools in place. These new competences become even more important as many countries within the ICES Area are now embarking on new policies.
Analysis of Arabidopsis genome-wide variations before and after meiosis and meiotic recombination by resequencing Landsberg erecta and all four products of a single meiosis
Authors: Lu Pingli , Han Xinwei , Qi Ji , Yang Jiange , Wijeratne Asela J. , Li Tao , Ma Hong
Published: November 2011

Meiotic recombination, including crossovers (COs) and gene conversions (GCs), impacts natural variation and is an important evolutionary force. COs increase genetic diversity by redistributing existing variation, whereas GCs can alter allelic frequency. Here, we sequenced Arabidopsis Landsberg erecta (Ler) and two sets of all four meiotic products from a Columbia (Col)/Ler hybrid to investigate genome-wide variation and meiotic recombination at nucleotide resolution. Comparing Ler and Col sequences uncovered 349,171 Single Nucleotide Polymorphisms (SNPs), 58,085 small and 2315 large insertions/deletions (indels), with highly correlated genome-wide distributions of SNPs, and small indels. A total of 443 genes have at least 10 nonsynonymous substitutions in protein-coding regions, with enrichment for disease-resistance genes. Another 316 genes are affected by large indels, including 130 genes with complete deletion of coding regions in Ler. Using the Arabidopsis qrt1 mutant, two sets of four meiotic products were generated and analyzed by sequencing for meiotic recombination, representing the first tetrad analysis with whole-genome sequencing in a nonfungal species. We detected 18 COs, six of which had an associated GC event, and four GCs without COs (NCOs), and revealed that Arabidopsis GCs are likely fewer and with shorter tracts than those in yeast. Meiotic recombination and chromosome assortment events dramatically redistributed genome variation in meiotic products, contributing to population diversity. In particular, meiosis provides a rapid mechanism to generate copy-number variation (CNV) of sequences that have different chromosomal positions in Col and Ler.
Hmga1 is differentially expressed and mediates silencing of the CD4/CD8 loci in T cell lineages and leukemic cells
Authors: Xi Yang , Watanabe Sugiko , Hino Yuko , Sakamoto Chiyomi , Nakatsu Yuko , Okada Seiji , Nakao Mitsuyoshi
Published: November 2011

High‐mobility group A1 (Hmga1) protein is an architectural chromatin factor, and aberrant Hmga1 expression in mice causes hematopoietic malignancies with defects in cellular differentiation. However, the functional involvement of Hmga1 in hematopoietic development and leukemic cells remains to be elucidated. Using Hmga1‐green fluorescent protein (GFP) knock‐in mice that endogenously express an Hmga1‐GFP fusion protein, we examined Hmga1 expression in undifferentiated and differentiated populations of hematopoietic cells. During early T cell development in the thymus, Hmga1 is highly expressed in CD4/CD8‐double negative (DN) cells and is transiently downregulated in CD4/CD8‐double positive (DP) cells. Consistently, Hmga1 directly binds to cis‐regulatory elements in the CD4/CD8 loci and the heterochromatin foci in DN‐stage cells, but not in DP cells. Interestingly, CD4/CD8 expression in DN‐stage leukemic cells is induced by inhibition of Hmga1 binding to nuclear DNA or RNA interference‐mediated Hmga1 knockdown. In addition, Hmga1‐depleted leukemic T cells markedly diminish proliferation, with transcriptional activation of cyclin‐dependent kinase inhibitor genes as a direct target of Hmga1. The data in the present study reveal a role of Hmga1 in transcriptional silencing in T cell lineages and leukemic cells. (Cancer Sci 2012; 103: 439–447)