bluuebunny/crossref_metadata_2025 huggingface dataset:
Metamaterial-based wireless strain sensors
Authors: Melik Rohat , Unal Emre , Perkgoz Nihan Kosku , Puttlitz Christian , Demir Hilmi Volkan
Published: July 2009

We proposed and demonstrated metamaterial-based strain sensors that are highly sensitive to mechanical deformation. Their resonance frequency shift is correlated with the surface strain of our test material and the strain data are reported telemetrically. These metamaterial sensors are better than traditional radio-frequency (rf) structures in sensing for providing resonances with high quality factors and large transmission dips. Using split ring resonators (SRRs), we achieve lower resonance frequencies per unit area compared to other rf structures, allowing for bioimplant sensing in soft tissue (e.g., fracture healing). In 5×5 SRR architecture, our wireless sensors yield high sensitivity (109 kHz/kgf, or 5.148 kHz/microstrain) with low nonlinearity error (<200 microstrain).
Chiral electron transport: Scattering through helical potentials
Authors: Yeganeh Sina , Ratner Mark A. , Medina Ernesto , Mujica Vladimiro
Published: July 2009

We present a model for the transmission of spin-polarized electrons through oriented chiral molecules, where the chiral structure is represented by a helix. The scattering potential contains a confining term and a spin-orbit contribution that is responsible for the spin-dependent scattering of electrons by the molecular target. The differential scattering cross section is calculated for right- and left-handed helices and for arbitrary electron spin polarizations. We apply our model to explain chiral effects in the intensity of photoemitted polarized electrons transmitted through thin organic layers. These are molecular interfaces that exhibit spin-selective scattering with surprisingly large asymmetry factors as well as a number of remarkable magnetic properties. In our model, differences in intensity are generated by the preferential transmission of electron beams whose polarization is oriented in the same direction as the sense of advance of the helix. This model can be easily extended to the Landauer regime of conductance where conductance is due to elastic scattering, so that we can consider the conductance of chiral molecular junctions.
In vivo nanomechanical imaging of blood-vessel tissues directly in living mammals using atomic force microscopy
Authors: Mao Youdong , Sun Quanmei , Wang Xiufeng , Ouyang Qi , Han Li , Jiang Lei , Han Dong
Published: July 2009

Atomic force microscopy (AFM) is difficult to achieve in living mammals but is necessary for understanding mechanical properties of tissues in their native form in organisms. Here we report in vivo nanomechanical imaging of blood-vessel tissues directly in living mammalians by AFM combined with surgical operations. Nanomechanical heterogeneity of blood vessels is observed across the diverse microenvironments of the same tissues in vivo. This method is further used to measure the counteractive nanomechanical changes in real time during drug-induced vasodilation and vasoconstriction in vivo, demonstrating appealing potential in characterization of in vivo nanomechanical dynamics of native tissues.
Giant birefringence induced by plasmonic nanoslit arrays
Authors: Hsu Shen-Yu , Lee Kuang-Li , Lin En-Hong , Lee Ming-Chang , Wei Pei-Kuen
Published: July 2009

Large phase differences between transverse electric (TE) and transverse magnetic (TM) waves were investigated in plasmonic nanoslit arrays. The phase of the TE wave shifts ahead because of its low propagation constant. On the other hand, the phase of the TM wave is retarded due to the propagation of surface plasmons. The opposite phase shift forms a giant birefringence. Its magnitude was dependent on the width of nanoslits. The birefringence magnitude was ∼1 for 300-nm-wide nanoslits and up to ∼2.7 for 100 nm ones. The spectroscopic measurements indicate that waveplates made of gold nanoslits have large bandwidths.
Tunable interference of light behind subwavelength apertures
Authors: Gao Feng , Li De , Peng Ru-Wen , Hu Qing , Wei Kuang , Wang Q. J. , Zhu Y. Y. , Wang Mu
Published: July 2009

We demonstrate in this letter that electromagnetic waves passing through the subwavelength apertures on a silver film interfere with each other in the airgap behind the apertures. Depending on the width of the airgap, either constructive or destructive interference occurs. It is shown that constructive interference enhances the extraordinary optical transmission and evidently improves the quality factor, whereas destructive interference weakens the extraordinary optical transmission. We suggest that our results provide a unique approach to construct plasmonic structures and devices.
Electrical characterization of the soft breakdown failure mode in MgO layers
Authors: Miranda E. , O’Connor E. , Cherkaoui K. , Monaghan S. , Long R. , O’Connell D. , Hurley P. K. , Hughes G. , Casey P.
Published: July 2009

The soft breakdown (SBD) failure mode in 20 nm thick MgO dielectric layers grown on Si substrates was investigated. We show that during a constant voltage stress, charge trapping and progressive breakdown coexist, and that the degradation dynamics is captured by a power-law time dependence. We also show that the SBD current-voltage (I-V) characteristics follow the power-law model I=aVb typical of this conduction mechanism but in a wider voltage window than the one reported in the past for SiO2. The relationship between the magnitude of the current and the normalized differential conductance was analyzed.
Crystal orientation of GaAs islands grown on SrTiO3 (001) by molecular beam epitaxy
Authors: Largeau L. , Cheng J. , Regreny P. , Patriarche G. , Benamrouche A. , Robach Y. , Gendry M. , Hollinger G. , Saint-Girons G.
Published: July 2009

The growth of GaAs islands on (001)-oriented SrTiO3 (STO) substrates by molecular beam epitaxy is studied. A competition between (111)- and (001)-oriented islands takes place. It is shown that this competition is driven by the interface energy and the critical nucleation volume of the GaAs/STO system. Perspectives are proposed to control this competition in order to define reliable growth procedures for the monolithic integration of GaAs based heterostructures on crystalline STO/Si(001) templates.
Multiband left-handed metamaterials
Authors: Wang Jiafu , Qu Shabo , Yang Yiming , Ma Hua , Wu Xiang , Xu Zhuo
Published: July 2009

A method of realizing multiband left-handed metamaterials (MB-LHMs) was presented. By alternatively stacking arrays of unit cells with different geometrical dimensions, the combined structures exhibit multiple LH passbands. As an example, a typical MB-LHM was designed, fabricated, and investigated numerically and experimentally. Both the simulation and experiment results show that the MB-LHM has three alternatively left- and right-handed passbands, of which two are LH ones.
Charging effect and capacitance modulation of Ni-rich NiO thin film
Authors: Ang R. , Chen T. P. , Liu Z. , Wong J. I. , Yi M. D. , Yang M. , Cen Z. H. , Zhu S. , Zhu W. , Goh E. S. M.
Published: July 2009

In this letter, Ni-rich NiO thin film is deposited on p-type Si substrate by dc magnetron sputtering to form a metal-insulator-semiconductor structure. The charge trapping in the Ni nanocrystals (nc-Ni) embedded in NiO matrix induces a flatband voltage shift and capacitance modulation, which could be used for memory applications. The charging of nc-Ni depends on the voltage polarity, as well as the charging time and magnitude of gate voltage. The capacitance modulation can be described by an equivalent circuit model.
Nanodomains in Fe+3-doped lead zirconate titanate ceramics at the morphotropic phase boundary do not correlate with high properties
Authors: Jin Li , He Zhanbing , Damjanovic Dragan
Published: July 2009

Configuration of domain walls in undoped and Fe+3-doped lead zirconate titanate (PZT) ceramics at the morphotropic phase boundary has been investigated by the transmission electron microscopy. The distance between domain walls in undoped PZT is on the order of hundreds of nanometers and is drastically reduced to tens of nanometers by acceptor doping. The properties of doped and undoped samples are compared and discussed in terms of domain size, phase mixture, and presence of dopants. It is suggested that the small domain size cannot be a dominant effect in the enhancement of the properties in morphotropic PZT.
Multiferroic oxides-based flash memory and spin-field-effect transistor
Authors: Jia Chenglong , Berakdar Jamal
Published: July 2009

We propose a modified spin-field-effect transistor fabricated in a two dimensional electron gas (2DEG) formed at the surface of multiferroic oxides with a transverse helical magnetic order. The topology of the oxide local magnetic moments induces a resonant momentum-dependent effective spin-orbit interaction acting on 2DEG. We show that spin polarization dephasing is strongly suppressed, which is crucial for functionality. The carrier spin precession phase depends linearly on the magnetic spiral helicity. The latter is electrically controllable by virtue of the magneto-electric effect. We also suggest a flash-memory device based on this structure.
Comparison of manual assessments of ewe fat reserves for on-farm use
Authors: Shands C. G. , McLeod B. , Lollback M. L. , Duddy G. , Hatcher S. , O'Halloran W. J.
Published: July 2009

The two systems currently used in Australia for assessing the body reserves of live sheep (fat and condition scoring) were evaluated for their ability to quantify the range of scores within a mob and their ability to discriminate between sheep of varying fatness. Three ewe genotypes (fine Merino, medium Merino and first-cross Border Leicester × Merino) were independently assessed by four assessors experienced in each system (i.e. eight assessors). Twenty-four hours after assessment the ewes were slaughtered in a commercial abattoir and hot carcass measures of tissue depth at the GR site (thickness of tissue over the 12th rib, 110mm from the midline) taken to allow correlation with the assessed live scores. There was at least three times more phenotypic variation in fat score assessment compared with condition score as the fat score assessors used a wider range of scores. Despite this the average repeatability of fat scoring (0.73–0.85) was greater than condition scoring (0.64–0.84) particularly within the fine Merino genotype. Although there was a strong linear relationship between assessments of fat and condition scoring, the regression coefficients comparing the two scoring systems indicated a greater discrimination among animals on fat score across all three genotypes. Furthermore the fat scores had a significantly higher correlation with GR tissue depth measured on the carcass than condition scores. These data indicate that both systems will similarly assess the average body fat reserves of a mob or animals; however, fat scoring achieves greater discrimination when the goal is to identify individuals that are lower or higher than the mob average.
A simplest steady-state Munch-like model of phloem translocation, with source and pathway and sink
Authors: Pickard William F. , Abraham-Shrauner Barbara
Published: July 2009

In the 80 years since its introduction by Münch, the pressure-driven mass-flow model of phloem translocation has become hegemonic, and has been mathematically modelled in many different fashions but not, to our knowledge, by one that incorporated the equations of hydrodynamics with those of osmosis and slice-source and slice-sink boundary conditions to yield a system that admits of an analytical steady-state solution for the sap velocity in a single sieve tube. To overcome this situation, we drastically simplified the problem by: (i) justifying a low Peclet number idealisation in which transverse variations could be neglected; (ii) justifying a low viscosity idealisation in which axial pressure drops could be neglected; and (iii) assuming a sink of strength sufficient to lower the photosynthate concentration at the extreme distal end of the sieve tube to levels at which it became unimportant. The resulting ordinary nonlinear second-order differential equation in sap velocity and axial position was of a generalised Liénard form with a single forcing parameter; and this is reason enough for the lack of a known analytic solution. However, since the forcing parameter was very large, it was possible to deduce approximate second-order solutions for behavior in the source, sink and transport regions: the sap velocity is zero at the slice-source, climbs with exponential rapidity to a plateau, maintains this plateau over most of the sieve tube, and then drops with exponential rapidity to zero at the slice-sink.
In-situ measurements of the mixing state and optical properties of soot with implications for radiative forcing estimates
Authors: Moffet Ryan C. , Prather Kimberly A.
Published: July 2009

Our ability to predict how global temperatures will change in the future is currently limited by the large uncertainties associated with aerosols. Soot aerosols represent a major research focus as they influence climate by absorbing incoming solar radiation resulting in a highly uncertain warming effect. The uncertainty stems from the fact that the actual amount soot warms our atmosphere strongly depends on the manner and degree in which it is mixed with other species, a property referred to as mixing state. In global models and inferences from atmospheric heating measurements, soot radiative forcing estimates currently differ by a factor of 6, ranging between 0.2–1.2 W/m2, making soot second only to CO2in terms of global warming potential. This article reports coupled in situ measurements of the size-resolved mixing state, optical properties, and aging timescales for soot particles. Fresh fractal soot particles dominate the measured absorption during peak traffic periods (6–9 AM local time). Immediately after sunrise, soot particles begin to age by developing a coating of secondary species including sulfate, ammonium, organics, nitrate, and water. Based on these direct measurements, the core-shell arrangement results in a maximum absorption enhancement of 1.6× over fresh soot. These atmospheric observations help explain the larger values for soot forcing measured by others and will be used to obtain closure in optical property measurements to reduce one of the largest remaining uncertainties in climate change.
Insertion of short transmembrane helices by the Sec61 translocon
Authors: Jaud Simon , Fernández-Vidal Mónica , Nilsson IngMarie , Meindl-Beinker Nadja M. , Hübner Nadja C. , Tobias Douglas J. , von Heijne Gunnar , White Stephen H.
Published: July 2009

The insertion efficiency of transmembrane (TM) helices by the Sec61 translocon depends on helix amino acid composition, the positions of the amino acids within the helix, and helix length. We have used an in vitro expression system to examine systematically the insertion efficiency of short polyleucine segments (L

n

,
n
= 4 … 12) flanked at either end by 4-residue sequences of the form XXPX-L

n

-XPXX with X = G, N, D, or K. Except for X = K, insertion efficiency (
p
) is <10% for
n
< 8, but rises steeply to 100% for
n
= 12. For X = K,
p
is already close to 100% for
n
= 10. A similar pattern is observed for synthetic peptides incorporated into oriented phospholipid bilayer arrays, consistent with the idea that recognition of TM segments by the translocon critically involves physical partitioning of nascent peptide chains into the lipid bilayer. Molecular dynamics simulations suggest that insertion efficiency is determined primarily by the energetic cost of distorting the bilayer in the vicinity of the TM helix. Very short lysine-flanked leucine segments can reduce the energetic cost by extensive hydrogen bonding with water and lipid phosphate groups (snorkeling) and by partial unfolding.
NPAS3 is a trachealess homolog critical for lung development and homeostasis
Authors: Zhou Shutang , Degan Simone , Potts Erin N. , Foster W. Michael , Sunday Mary E.
Published: July 2009

Trachealess (Trh) is a PAS domain transcription factor regulating
Drosophila
tracheogenesis. No other Trh homolog has been associated with a respiratory phenotype. Seeking homolog(s) regulating lung development, we screened murine genomic DNA using
trh
oligonucleotides, identifying only
Npas3. Npas3
mRNA peaks in lung from E10.5 to E13.5, verified by sequencing, with immunostaining in airway epithelial cells.
Npas3
-null mice have reduced lung branching morphogenesis but are viable prenatally.
Npas3
-null newborns die in respiratory distress, with diminished alveolarization, decreased
Shh
,
Fgf9
,
Fgf10
, and
Bmp4
mRNAs, and increased
Spry2
, consistent with reduced FGF signaling. Exogenous FGF10 rescues branching morphogenesis in
Npas3
-null lungs. In promoter reporter assays, NPAS3 directly upregulates
Shh
and represses
Spry2. Npas3
+/−
mice have a milder lung phenotype, surviving postnatally, but develop emphysema. Therefore, absence of a developmentally expressed transcription factor can alter downstream gene expression and multiple signaling pathways in organogenesis. NPAS3 haploinsufficiency may also lead to emphysema.
A
Drosophila
model identifies calpains as modulators of the human leukemogenic fusion protein AML1-ETO
Authors: Osman Dani , Gobert Vanessa , Ponthan Frida , Heidenreich Olaf , Haenlin Marc , Waltzer Lucas
Published: July 2009

The t(8:21)(q22;q22) translocation is 1 of the most common chromosomal abnormalities linked to acute myeloid leukemia (AML). AML1-ETO, the product of this translocation, fuses the N-terminal portion of the RUNX transcription factor AML1 (also known as RUNX1), including its DNA-binding domain, to the almost entire transcriptional corepressor ETO (also known as MTG8 or RUNX1T1). This fusion protein acts primarily by interfering with endogenous AML1 function during myeloid differentiation, although relatively few genes are known that participate with AML1-ETO during leukemia progression. Here, we assessed the consequences of expressing this chimera in
Drosophila
blood cells. Reminiscent of what is observed in AML, AML1-ETO specifically inhibited the differentiation of the blood cell lineage whose development depends on the RUNX factor Lozenge (LZ) and induced increased numbers of LZ
+
progenitors. Using an in vivo RNAi-based screen for suppressors of AML1-ETO, we identified
calpainB
as required for AML1-ETO-induced blood cell disorders in
Drosophila
. Remarkably, calpain inhibition triggered AML1-ETO degradation and impaired the clonogenic potential of the human t(8;21) leukemic blood cell line Kasumi-1. Therefore
Drosophila
provides a promising genetically tractable model to investigate the conserved basis of leukemogenesis and to open avenues in AML therapy.
Dynamics of locking of peptides onto growing amyloid fibrils
Authors: Reddy Govardhan , Straub John E. , Thirumalai D.
Published: July 2009

Sequence-dependent variations in the growth mechanism and stability of amyloid fibrils, which are implicated in a number of neurodegenerative diseases, are poorly understood. We have carried out extensive all-atom molecular dynamics simulations to monitor the structural changes that occur upon addition of random coil (RC) monomer fragments from the yeast prion Sup35 and Aβ-peptide onto a preformed fibril. Using the atomic resolution structures of the microcrystals as the starting points, we show that the RC → β-strand transition for the Sup35 fragment occurs abruptly over a very narrow time interval, whereas the acquisition of strand content is less dramatic for the hydrophobic-rich Aβ-peptide. Expulsion of water, resulting in the formation of a dry interface between 2 adjacent sheets of the Sup35 fibril, occurs in 2 stages. Ejection of a small number of discrete water molecules in the second stage follows a rapid decrease in the number of water molecules in the first stage. Stability of the Sup35 fibril is increased by a network of hydrogen bonds involving both backbone and side chains, whereas the marginal stability of the Aβ-fibrils is largely due to the formation of weak dispersion interaction between the hydrophobic side chains. The importance of the network of hydrogen bonds is further illustrated by mutational studies, which show that substitution of the Asn and Gln residues to Ala compromises the Sup35 fibril stability. Despite the similarity in the architecture of the amyloid fibrils, the growth mechanism and stability of the fibrils depend dramatically on the sequence.
Loss of phosphatidylinositol 4-kinase 2α activity causes late onset degeneration of spinal cord axons
Authors: Simons J. Paul , Al-Shawi Raya , Minogue Shane , Waugh Mark G. , Wiedemann Claudia , Evangelou Stylianos , Loesch Andrzej , Sihra Talvinder S. , King Rosalind , Warner Thomas T. , Hsuan J. Justin
Published: July 2009

Phosphoinositide (PI) lipids are intracellular membrane signaling intermediates and effectors produced by localized PI kinase and phosphatase activities. Although many signaling roles of PI kinases have been identified in cultured cell lines, transgenic animal studies have produced unexpected insight into the in vivo functions of specific PI 3- and 5-kinases, but no mammalian PI 4-kinase (PI4K) knockout has previously been reported. Prior studies using cultured cells implicated the PI4K2α isozyme in diverse functions, including receptor signaling, ion channel regulation, endosomal trafficking, and regulated secretion. We now show that despite these important functions, mice lacking PI4K2α kinase activity initially appear normal. However, adult

Pi4k2a
GT/GT

animals develop a progressive neurological disease characterized by tremor, limb weakness, urinary incontinence, and premature mortality. Histological analysis of aged

Pi4k2a
GT/GT

animals revealed lipofuscin-like deposition and gliosis in the cerebellum, and loss of Purkinje cells. Peripheral nerves are essentially normal, but massive axonal degeneration was found in the spinal cord in both ascending and descending tracts. These results reveal a previously undescribed role for aberrant PI signaling in neurological disease that resembles autosomal recessive hereditary spastic paraplegia.
Prosaposin inhibits tumor metastasis via paracrine and endocrine stimulation of stromal p53 and Tsp-1
Authors: Kang Soo-Young , Halvorsen Ole J. , Gravdal Karsten , Bhattacharya Nandita , Lee Jung Min , Liu Nathan W. , Johnston Brian T. , Johnston Adam B. , Haukaas Svein A. , Aamodt Kristie , Yoo Sun , Akslen Lars A. , Watnick Randolph S.
Published: July 2009

Metastatic tumors can prepare a distant site for colonization via the secretion of factors that act in a systemic manner. We hypothesized that non- or weakly metastatic human tumor cells may act in an opposite fashion by creating a microenvironment in distant tissues that is refractory to colonization. By comparing cell lines with different metastatic potential, we have identified a tumor-secreted inhibitor of metastasis, prosaposin (Psap), which functions in a paracrine and endocrine fashion by stimulating the expression of thrombospondin-1 (Tsp-1) in fibroblasts present in both primary tumors and distant organs, doing so in a p53-dependent manner. Introduction of Psap in highly metastatic cells significantly reduced the occurrence of metastases, whereas inhibition of Psap production by tumor cells was associated with increased metastatic frequency. In human prostate cancer, decreased Psap expression was significantly associated with metastatic tumors. Our findings suggest that prosaposin, or other agents that stimulate p53 activity in the tumor stroma, may be an effective therapy by inhibition of the metastatic process.
Genetic screen identifies serpin5 as a regulator of the toll pathway and CHMP2B toxicity associated with frontotemporal dementia
Authors: Ahmad S. Tariq , Sweeney Sean T. , Lee Jin-A , Sweeney Neal T. , Gao Fen-Biao
Published: July 2009

Frontotemporal dementia (FTD) is the most common form of dementia before 60 years of age. Rare pathogenic mutations in
CHMP2B
, which encodes a component of the endosomal sorting complex required for transport (ESCRT-III), are associated with FTD linked to chromosome 3 (FTD3). Animal models of FTD3 have not yet been reported, and what signaling pathways are misregulated by mutant CHMP2B in vivo is unknown. Here we report the establishment of a
Drosophila
model of FTD3 and show the genetic interactions between mutant CHMP2B and other components of ESCRT. Through an unbiased genome-wide screen, we identified 29 modifier loci and found that serpin5 (Spn5), a largely uncharacterized serine protease inhibitor, suppresses the melanization phenotype induced by mutant CHMP2B in the fly eye. We also found that Spn5 is a negative regulator of the Toll pathway and functions extracellularly, likely by blocking the proteolytic activation of Spaetzle, the Toll receptor ligand. Moreover, Spn5 inhibited activation of the Toll pathway by mutant CHMP2B. Our findings identify Spn5 as a regulator of the Toll pathway and CHMP2B toxicity and show that the Toll pathway is a major signaling pathway misregulated by mutant CHMP2B in vivo. This fly model will be useful to further dissect genetic pathways that are potentially relevant to the pathogenesis and treatment of FTD.
Probing the role of the cation–π interaction in the binding sites of GPCRs using unnatural amino acids
Authors: Torrice Michael M. , Bower Kiowa S. , Lester Henry A. , Dougherty Dennis A.
Published: July 2009

We describe a general application of the nonsense suppression methodology for unnatural amino acid incorporation to probe drug–receptor interactions in functional G protein-coupled receptors (GPCRs), evaluating the binding sites of both the M2 muscarinic acetylcholine receptor and the D2 dopamine receptor. Receptors were expressed inXenopusoocytes, and activation of a G protein-coupled, inward-rectifying K+channel (GIRK) provided, after optimization of conditions, a quantitative readout of receptor function. A number of aromatic amino acids thought to be near the agonist-binding site were evaluated. Incorporation of a series of fluorinated tryptophan derivatives at W6.48 of the D2 receptor establishes a cation–π interaction between the agonist dopamine and W6.48, suggesting a reorientation of W6.48 on agonist binding, consistent with proposed “rotamer switch” models. Interestingly, no comparable cation–π interaction was found at the aligning residue in the M2 receptor.
Resources and energetics determined dinosaur maximal size
Authors: McNab Brian K.
Published: July 2009

Some dinosaurs reached masses that were ≈8 times those of the largest, ecologically equivalent terrestrial mammals. The factors most responsible for setting the maximal body size of vertebrates are resource quality and quantity, as modified by the mobility of the consumer, and the vertebrate's rate of energy expenditure. If the food intake of the largest herbivorous mammals defines the maximal rate at which plant resources can be consumed in terrestrial environments and if that limit applied to dinosaurs, then the large size of sauropods occurred because they expended energy in the field at rates extrapolated from those of varanid lizards, which are ≈22% of the rates in mammals and 3.6 times the rates of other lizards of equal size. Of 2 species having the same energy income, the species that uses the most energy for mass-independent maintenance of necessity has a smaller size. The larger mass found in some marine mammals reflects a greater resource abundance in marine environments. The presumptively low energy expenditures of dinosaurs potentially permitted Mesozoic communities to support dinosaur biomasses that were up to 5 times those found in mammalian herbivores in Africa today. The maximal size of predatory theropods was ≈8 tons, which if it reflected the maximal capacity to consume vertebrates in terrestrial environments, corresponds in predatory mammals to a maximal mass less than a ton, which is what is observed. Some coelurosaurs may have evolved endothermy in association with the evolution of feathered insulation and a small mass.
Neuroprotective natural antibodies to assemblies of amyloidogenic peptides decrease with normal aging and advancing Alzheimer's disease
Authors: Britschgi M. , Olin C. E. , Johns H. T. , Takeda-Uchimura Y. , LeMieux M. C. , Rufibach K. , Rajadas J. , Zhang H. , Tomooka B. , Robinson W. H. , Clark C. M. , Fagan A. M. , Galasko D. R. , Holtzman D. M. , Jutel M. , Kaye J. A. , Lemere C. A. , Leszek J. , Li G. , Peskind E. R. , Quinn J. F. , Yesavage J. A. , Ghiso J. A. , Wyss-Coray T.
Published: July 2009

A number of distinct β-amyloid (Aβ) variants or multimers have been implicated in Alzheimer's disease (AD), and antibodies recognizing such peptides are in clinical trials. Humans have natural Aβ-specific antibodies, but their diversity, abundance, and function in the general population remain largely unknown. Here, we demonstrate with peptide microarrays the presence of natural antibodies against known toxic Aβ and amyloidogenic non-Aβ species in plasma samples and cerebrospinal fluid of AD patients and healthy controls aged 21–89 years. Antibody reactivity was most prominent against oligomeric assemblies of Aβ and pyroglutamate or oxidized residues, and IgGs specific for oligomeric preparations of Aβ1-42 in particular declined with age and advancing AD. Most individuals showed unexpected antibody reactivities against peptides unique to autosomal dominant forms of dementia (mutant Aβ, ABri, ADan) and IgGs isolated from plasma of AD patients or healthy controls protected primary neurons from Aβ toxicity. Aged vervets showed similar patterns of plasma IgG antibodies against amyloid peptides, and after immunization with Aβ the monkeys developed high titers not only against Aβ peptides but also against ABri and ADan peptides. Our findings support the concept of conformation-specific, cross-reactive antibodies that may protect against amyloidogenic toxic peptides. If a therapeutic benefit of Aβ antibodies can be confirmed in AD patients, stimulating the production of such neuroprotective antibodies or passively administering them to the elderly population may provide a preventive measure toward AD.
Predicting Social Security numbers from public data
Authors: Acquisti Alessandro , Gross Ralph
Published: July 2009

Information about an individual's place and date of birth can be exploited to predict his or her Social Security number (SSN). Using only publicly available information, we observed a correlation between individuals' SSNs and their birth data and found that for younger cohorts the correlation allows statistical inference of private SSNs. The inferences are made possible by the public availability of the Social Security Administration's Death Master File and the widespread accessibility of personal information from multiple sources, such as data brokers or profiles on social networking sites. Our results highlight the unexpected privacy consequences of the complex interactions among multiple data sources in modern information economies and quantify privacy risks associated with information revelation in public forums.
Insights into the molecular architecture of the 26S proteasome
Authors: Nickell Stephan , Beck Florian , Scheres Sjors H. W. , Korinek Andreas , Förster Friedrich , Lasker Keren , Mihalache Oana , Sun Na , Nagy István , Sali Andrej , Plitzko Jürgen M. , Carazo Jose-Maria , Mann Matthias , Baumeister Wolfgang
Published: July 2009

Cryo-electron microscopy in conjunction with advanced image analysis was used to analyze the structure of the 26S proteasome and to elucidate its variable features. We have been able to outline the boundaries of the ATPase module in the “base” part of the regulatory complex that can vary in its position and orientation relative to the 20S core particle. This variation is consistent with the “wobbling” model that was previously proposed to explain the role of the regulatory complex in opening the gate in the α-rings of the core particle. In addition, a variable mass near the mouth of the ATPase ring has been identified as Rpn10, a multiubiquitin receptor, by correlating the electron microscopy data with quantitative mass spectrometry.
Beyond the Consulting Room: Intuition and Intersubjectivity in Journal Peer Review
Authors: Lipworth Wendy
Published: July 2009

Objective: The manuscript review process is a central part of medicine, but has become increasingly the subject of criticism. A frequent claim is that the process is insufficiently objective and that it is inconsistent in its capacity to assess manuscript quality. Implicit in this is the expectation that manuscript review is, or should be, a ‘scientific’ process. In this paper I examine and critique this ‘scientific imperative’.

Conclusions: Manuscript review, like clinical medicine and (ironically) like science itself, is not and cannot be a ‘scientific’ process, and this needs to be taken into account both by those carrying out reviews and those who wish to evaluate and improve the manuscript review process.
Suppression of RhoG activity is mediated by a syndecan 4–synectin–RhoGDI1 complex and is reversed by PKCα in a Rac1 activation pathway
Authors: Elfenbein Arye , Rhodes John M. , Meller Julia , Schwartz Martin A. , Matsuda Michiyuki , Simons Michael
Published: July 2009

Fibroblast growth factor 2 (FGF2) is a major regulator of developmental, pathological, and therapeutic angiogenesis. Its activity is partially mediated by binding to syndecan 4 (S4), a proteoglycan receptor. Angiogenesis requires polarized activation of the small guanosine triphosphatase Rac1, which involves localized dissociation from RhoGDI1 and association with the plasma membrane. Previous work has shown that genetic deletion of S4 or its adapter, synectin, leads to depolarized Rac activation, decreased endothelial migration, and other physiological defects. In this study, we show that Rac1 activation downstream of S4 is mediated by the RhoG activation pathway. RhoG is maintained in an inactive state by RhoGDI1, which is found in a ternary complex with synectin and S4. Binding of S4 to synectin increases the latter's binding to RhoGDI1, which in turn enhances RhoGDI1's affinity for RhoG. S4 clustering activates PKCα, which phosphorylates RhoGDI1 at Ser96. This phosphorylation triggers release of RhoG, leading to polarized activation of Rac1. Thus, FGF2-induced Rac1 activation depends on the suppression of RhoG by a previously uncharacterized ternary S4–synectin–RhoGDI1 protein complex and activation via PKCα.
Synchronizing chromosome segregation by flux-dependent force equalization at kinetochores
Authors: Matos Irina , Pereira António J. , Lince-Faria Mariana , Cameron Lisa A. , Salmon Edward D. , Maiato Helder
Published: July 2009

The synchronous movement of chromosomes during anaphase ensures their correct inheritance in every cell division. This reflects the uniformity of spindle forces acting on chromosomes and their simultaneous entry into anaphase. Although anaphase onset is controlled by the spindle assembly checkpoint, it remains unknown how spindle forces are uniformly distributed among different chromosomes. In this paper, we show that tension uniformity at metaphase kinetochores and subsequent anaphase synchrony in Drosophila S2 cells are promoted by spindle microtubule flux. These results can be explained by a mechanical model of the spindle where microtubule poleward translocation events associated with flux reflect relaxation of the kinetochore–microtubule interface, which accounts for the redistribution and convergence of kinetochore tensions in a timescale comparable to typical metaphase duration. As predicted by the model, experimental acceleration of mitosis precludes tension equalization and anaphase synchrony. We propose that flux-dependent equalization of kinetochore tensions ensures a timely and uniform maturation of kinetochore–microtubule interfaces necessary for error-free and coordinated segregation of chromosomes in anaphase.
Increased NOD2-mediated recognition of N-glycolyl muramyl dipeptide
Authors: Coulombe François , Divangahi Maziar , Veyrier Frédéric , de Léséleuc Louis , Gleason James L. , Yang Yibin , Kelliher Michelle A. , Pandey Amit K. , Sassetti Christopher M. , Reed Michael B. , Behr Marcel A.
Published: July 2009

Peptidoglycan-derived muramyl dipeptide (MDP) activates innate immunity via the host sensor NOD2. Although MDP is N-acetylated in most bacteria, mycobacteria and related Actinomycetes convert their MDP to an N-glycolylated form through the action of N-acetyl muramic acid hydroxylase (NamH). We used a combination of bacterial genetics and synthetic chemistry to investigate whether N-glycolylation of MDP alters NOD2-mediated immunity. Upon infecting macrophages with 12 bacteria, tumor necrosis factor (TNF) α secretion was NOD2 dependent only with mycobacteria and other Actinomycetes (Nocardia and Rhodococcus). Disruption of namH in Mycobacterium smegmatis obrogated NOD2-mediated TNF secretion, which could be restored upon gene complementation. In mouse macrophages, N-glycolyl MDP was more potent than N-acetyl MDP at activating RIP2, nuclear factor κB, c-Jun N-terminal kinase, and proinflammatory cytokine secretion. In mice challenged intraperitoneally with live or killed mycobacteria, NOD2-dependent immune responses depended on the presence of bacterial namH. Finally, N-glycolyl MDP was more efficacious than N-acetyl MDP at inducing ovalbumin-specific T cell immunity in a model of adjuvancy. Our findings indicate that N-glycolyl MDP has a greater NOD2-stimulating activity than N-acetyl MDP, consistent with the historical observation attributing exceptional immunogenic activity to the mycobacterial cell wall.
Risk Factors and Outcomes Associated with Isolation of Meropenem High-Level-Resistant Pseudomonas aeruginosa
Authors: Eagye Kathryn J. , Kuti Joseph L. , Nicolau David P.
Published: July 2009

Objective.

To determine risk factors and outcomes for patients with meropenem high–level-resistant Pseudomonas aeruginosa (MRPA) (minimum inhibitory concentration [MIC] ≥ 32 μg/mL).

Design.

Case-control-control.

Setting.

An 867-bed urban, teaching hospital.

Patients.

Fifty-eight MRPA case patients identified from an earlier P. aeruginosa study; 125 randomly selected control patients with meropenem-susceptible P. aeruginosa (MSPA) (MIC ≤ 4 μg/mL), and 57 control patients without P. aeruginosa (sampled by case date/location).

Methods.

Patient data, outcomes, and costs were obtained via administrative database. Cases were compared to each control group while controlling for time at risk (days between admission and culture, or entire length of stay [LOS] for patients without P. aeruginosa).

Results.

A multivariable model predicted risks for MRPA versus MSPA (odds ratio [95% confidence interval]): more admissions (in the prior 12 months) (1.41 [1.15, 1.74]), congestive heart failure (2.19 [1.03, 4.68]), and Foley catheter (2.53 [1.18, 5.45]) (adj. R2 = 0.28). For MRPA versus no P. aeruginosa, risks were age (in 5-year increments) (1.17 [1.03, 1.33]), more prior admissions (1.40 [1.08, 1.81]), and more days in the intensive care unit (1.10 [1.03, 1.18]) (adj. R2 = 0.32). Other invasive devices (including mechanical ventilation) and previous antibiotic use (including carbapenems) were nonsignificant. MRPA mortality (31%) did not differ from that of MSPA (15%) when adjusted for time at risk (P = .15) but did from mortality without P. aeruginosa (9%) (P = .01 ). Median LOS and costs were greater for MRPA patients versus MSPA patients and patients without P. aeruginosa: 30 days versus 16 and 10 (P < .01 ) and $88,425 versus $28,620 and $22,605 (P <.01).

Conclusions.

Although antibiotic use has been shown to promote resistance, our data found that prior antibiotic use was not associated with MRPA acquisition. However, admission frequency and Foley catheters were, suggesting that infection control measures are essential to reducing MRPA transmission.
Density profile peaking in JET H-mode plasmas: experiments versus linear gyrokinetic predictions
Authors: Maslov M. , Angioni C. , Weisen H.
Published: July 2009

As an independent complement to previous studies (Weisen et al
2005 Nucl. Fusion
45 L1–4, Weisen et al
2006 Plasma Phys. Control. Fusion
48 A457–66, Angioni et al
2007 Nucl. Fusion
47 1326–35), density peaking in the JET tokamak was investigated on the dataset, comprising virtually all H-mode experiments performed in 2006–2007. Unlike previous studies, this work focuses on low collisionality data as most representative of reactor conditions. The study confirms that collisionality is the most important parameter governing density peaking in H-mode, followed by the NBI particle flux and/or the T
i/T
e temperature ratio. For the first time in JET a modest, albeit significant dependence of peaking on internal inductance, or magnetic shear is seen. The experimental behaviour is compared with an extensive database of linear gyrokinetic calculations using the GS2 code. The predictions from GS2 simulations based on the highest linear growth rate mode are in good agreement with experimental observations. They are also corroborated by initial results from the non-linear code GYRO.
Equilibrium, flow shear and stability measurements in the Z-pinch
Authors: Shumlak U. , Adams C.S. , Blakely J.M. , Chan B.-J. , Golingo R.P. , Knecht S.D. , Nelson B.A. , Oberto R.J. , Sybouts M.R. , Vogman G.V.
Published: July 2009

The stabilizing effect of a sheared axial flow is investigated in the ZaP flow Z-pinch experiment at the University of Washington. Long-lived, hydrogen Z-pinch plasmas are generated that are 1 m long with an approximately 10 mm radius and exhibit gross stability for many Alfvén transit times. Large magnetic fluctuations occur during pinch assembly, after which the amplitude and frequency of the fluctuations diminish. This stable behaviour continues for an extended quiescent period. At the end of the quiescent period, fluctuation levels increase in magnitude and frequency. Axial flow profiles are determined by measuring the Doppler shift of plasma impurity lines using a 20-chord spectrometer. Experimental measurements show a sheared flow that is coincident with low magnetic fluctuations during the quiescent period. The experimental flow shear exceeds the theoretical threshold during the quiescent period, and the flow shear is lower than the theoretical threshold at other times. The observed plasma behaviour and correlation between the sheared flow and stability persists as the amount of injected neutral gas and experimental geometry are varied. Computer simulations using experimentally observed plasma profiles show a consistent sheared flow stabilization effect. Plasma pinch parameters are measured independently to demonstrate an equilibrium consistent with radial force balance.
Preliminary safety analysis for the Chinese ITER Dual Functional Lithium–Lead Test Blanket Module
Authors: Chen Hongli , Bai Yunqing , Hu Liqin , Chen Mingliang , Song Yong , Zeng Qin , Liu Songlin
Published: July 2009

Safety analysis is part of the ITER Test Blanket Module (TBM) design process ensuring that the TBM does not adversely affect the safety of ITER. To get the licence for TBM as a whole with ITER, relevant safety analysis is required for each TBM system proposed by each party. The safety analysis for the Chinese Dual Functional Lithium–Lead Test Blanket Module (DFLL-TBM) has been performed based on the latest DFLL-TBM design. In this paper, the following safety considerations, such as source terms, operational releases, accident sequence analyses and waste assessment, were analysed. Both the deterministic approach and the complementary systematic approach starting with failure mode and effects analysis studies were adopted in the accidental analysis. The preliminary results showed that the DFLL-TBM system at normal operating conditions and under accident scenarios did not add additional safety hazards to the ITER machine and could meet the ITER safety requirements and additional safety requirements for the TBM system.
Development and achievements on the high power ECRF system in JT-60U
Authors: Moriyama S. , Kobayashi T. , Isayama A. , Terakado M. , Sawahata M. , Suzuki S. , Yokokura K. , Shimono M. , Hasegawa K. , Hiranai S. , Igarashi K. , Sato F. , Suzuki T. , Wada K. , Shinozaki S. , Seki M. , Kasugai A. , Takahashi K. , Kajiwara K. , Sakamoto K. , Fujii T.
Published: July 2009

An output power of 1.5 MW for 1 s was achieved at 110 GHz in a recent gyrotron development using the JT-60U ECRF system. It is the world's highest power oscillation for a pulse duration of at least 1 s. The achievement was enabled by, in addition to the carefully designed cavity and collector, necessary because of thermal stress, an RF shield for the adjustment bellows and a low-dielectric-loss dc break. The way the power was modulated was improved upon by controlling the anode voltage, with high modulation frequency of 5 kHz being achieved in NTM stabilization experiments. Moreover, as a developmental step to realizing a reliable ECRF system for use in future fusion experiments, a long pulse demonstration of 0.4 MW and a 30 s injection into the plasma was achieved with real time control of the anode/cathode-heater. Confirmation was made that the temperature of the cooled components had been saturated with no evidence of any damage being discovered in the waveguides and antenna without forced cooling. An innovative antenna with a relatively wide range of beam steering capabilities utilizing a linearly moving-mirror concept was also designed for use as an active cooling antenna with longer pulses in the future, e.g. for JT-60SA. The beam profile and mechanical strength analyses proved the feasibility of the antenna.
High-resolution analysis of epigenetic changes associated with X inactivation
Authors: Marks Hendrik , Chow Jennifer C. , Denissov Sergei , Françoijs Kees-Jan , Brockdorff Neil , Heard Edith , Stunnenberg Hendrik G.
Published: July 2009

Differentiation of female murine ES cells triggers silencing of one X chromosome through X-chromosome inactivation (XCI). Immunofluorescence studies showed that soon after Xist RNA coating the inactive X (Xi) undergoes many heterochromatic changes, including the acquisition of H3K27me3. However, the mechanisms that lead to the establishment of heterochromatin remain unclear. We first analyze chromatin changes by ChIP-chip, as well as RNA expression, around the X-inactivation center (Xic) in female and male ES cells, and their day 4 and 10 differentiated derivatives. A dynamic epigenetic landscape is observed within the Xic locus. Tsix repression is accompanied by deposition of H3K27me3 at its promoter during differentiation of both female and male cells. However, only in female cells does an active epigenetic landscape emerge at the Xist locus, concomitant with high Xist expression. Several regions within and around the Xic show unsuspected chromatin changes, and we define a series of unusual loci containing highly enriched H3K27me3. Genome-wide ChIP-seq analyses show a female-specific quantitative increase of H3K27me3 across the X chromosome as XCI proceeds in differentiating female ES cells. Using female ES cells with nonrandom XCI and polymorphic X chromosomes, we demonstrate that this increase is specific to the Xi by allele-specific SNP mapping of the ChIP-seq tags. H3K27me3 becomes evenly associated with the Xi in a chromosome-wide fashion. A selective and robust increase of H3K27me3 and concomitant decrease in H3K4me3 is observed over active genes. This indicates that deposition of H3K27me3 during XCI is tightly associated with the act of silencing of individual genes across the Xi.