bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural and optical characterization of two-dimensional arrays of Si nanocrystals embedded in SiO2 for photovoltaic applications
Authors: Gardelis S. , Nassiopoulou A. G. , Manousiadis P. , Milita Silvia , Gkanatsiou A. , Frangis N. , Lioutas Ch. B.
Published: May 2012

We report on the structural and optical characterization of two-dimensional arrays of silicon nanocrystals (SiNCs) suitable for photovoltaic applications. Single and multiple SiNC layers were grown on quartz by low pressure chemical vapor deposition of Si and subsequent thermal oxidation steps. The single SiNC layers consisted of one SiNC layer embedded in two silicon dioxide (SiO2) layers, whereas the multi-layered structure consisted of five SiNC layers of equal thickness separated by SiO2 layers. SiNC layers with thicknesses ranging from 2 to 25 nm were investigated. A thorough structural characterization of the films was carried out by combining grazing incidence x-ray diffraction, x-ray reflectivity, and transmission electron microscopy (TEM). Both XRD and TEM measurements revealed that the SiNC layers were polycrystalline in nature and composed of SiNCs, separated by grain boundaries, with their vertical size equal to the SiNC layer and their lateral size characterized by a narrow size distribution. The high resolution TEM (HRTEM) images showed that oxidation of the SiNC layers proceeded by consumption of Si from their top surface, without any detectable oxidation at the grain boundaries. Only in the case of the thinnest investigated SiNC layer (2 nm), the SiNCs were well separated by SiO2 tunnel barriers. From transmission and reflection optical measurements, energy band gaps of the SiNCs were estimated. These results were correlated with the sizes of the SiNCs obtained by HRTEM. A shift of the estimated band gaps with decreasing SiNC size was observed. This was consistent with quantum size effects in the SiNCs. The film containing the smallest SiNCs (2 nm in the growth direction), besides a significant shift of the absorption edge to higher energies, showed light emission at room temperature which is due to radiative recombination of photo-generated carriers in localized SiNCs separated by SiO2 tunnel barriers.
Ultra-low-phase-noise cryocooled microwave dielectric-sapphire-resonator oscillators
Authors: Hartnett John G. , Nand Nitin R. , Lu Chuan
Published: May 2012

Two nominally identical ultra-stable microwave oscillators are compared. Each incorporates a sapphire resonator cooled to near 6 K in an ultra-low vibration cryostat using a pulse-tube cryocooler. The phase noise for a single oscillator is measured at −105 dBc/Hz at 1 Hz offset on the 11.2 GHz carrier. The oscillator fractional frequency stability, after subtracting a linear frequency drift of 3.5×10-14/day, is characterized by 5.3×10-16τ-1/2+9×10-17 for integration times 0.1s<τ<1000s and is limited by a flicker frequency noise floor near 1×10-16.
Large actuation and high dielectric strength in metallized dielectric elastomer actuators
Authors: Hsien Low Sze , Lynn Shiau Li , Lau Gih-Keong
Published: May 2012

Metal films are seldom used as compliant electrodes for dielectric elastomer actuator (DEA) because they tend to restrain deformation of soft dielectrics. This work showed that silver film electrodes formed by electroless deposition (ELD) are indeed stretchable, and the DEA using ELD silver electrodes is able to generate an actuation up to 50% areal strain. Such ELD silver electrodes can self-heal, remain conductive at up to 33% uni-axial strain, and do not stiffen the dielectric layer as much as the sputtered silver electrodes. This metallized DEA can sustain a high breakdown field up to 350 MV/m, which is good for generating a large actuation force.
Electron transport in suspended semiconductor structures with two-dimensional electron gas
Authors: Pogosov A. G. , Budantsev M. V. , Zhdanov E. Yu. , Pokhabov D. A. , Bakarov A. K. , Toropov A. I.
Published: May 2012

We study electron transport in suspended semiconductor microstructures fabricated from AlAs/GaAs membranes containing a high mobility two-dimensional electron gas. In quantizing magnetic fields, a reflection of edge current channels from the border of suspended area is observed resulting in the absence of vanishing magnetoresistance in the quantum Hall effect (QHE) regime. Relocation of this border out of the Hall bar revives the QHE. We have also found that the critical current of the breakdown of QHE in suspended samples is three times lower than in non-suspended samples due to the peculiarity of heat transport in the membranes.
Band gap engineering in BiNbO4 for visible-light photocatalysis
Authors: Wang B. C. , Nisar J. , Pathak B. , Kang T. W. , Ahuja R.
Published: May 2012

We have investigated the electronic structure of anionic mono- (S, N, and C) and co-doping (N-N, C-N, S-C, and S-N) on BiNbO4 for the visible-light photocatalysis. The maximum band gap reduction of pure BiNbO4 is possible with the (C-S) co-doping and minimum with N mono-doping. The calculated binding energies show that the co-doped systems are more stable than their mono-doped counterparts. Our optical absorption curves indicate that the mono- (C) and co-anionic doped (N-N and C-S) BiNbO4 systems are promising materials for visible light photocatalysis.
A programmable droplet-based microfluidic device applied to multiparameter analysis of single microbes and microbial communities
Authors: Leung Kaston , Zahn Hans , Leaver Timothy , Konwar Kishori M. , Hanson Niels W. , Pagé Antoine P. , Lo Chien-Chi , Chain Patrick S. , Hallam Steven J. , Hansen Carl L.
Published: May 2012

We present a programmable droplet-based microfluidic device that combines the reconfigurable flow-routing capabilities of integrated microvalve technology with the sample compartmentalization and dispersion-free transport that is inherent to droplets. The device allows for the execution of user-defined multistep reaction protocols in 95 individually addressable nanoliter-volume storage chambers by consecutively merging programmable sequences of picoliter-volume droplets containing reagents or cells. This functionality is enabled by “flow-controlled wetting,” a droplet docking and merging mechanism that exploits the physics of droplet flow through a channel to control the precise location of droplet wetting. The device also allows for automated cross-contamination-free recovery of reaction products from individual chambers into standard microfuge tubes for downstream analysis. The combined features of programmability, addressability, and selective recovery provide a general hardware platform that can be reprogrammed for multiple applications. We demonstrate this versatility by implementing multiple single-cell experiment types with this device: bacterial cell sorting and cultivation, taxonomic gene identification, and high-throughput single-cell whole genome amplification and sequencing using common laboratory strains. Finally, we apply the device to genome analysis of single cells and microbial consortia from diverse environmental samples including a marine enrichment culture, deep-sea sediments, and the human oral cavity. The resulting datasets capture genotypic properties of individual cells and illuminate known and potentially unique partnerships between microbial community members.
Kinetic mechanism for HIV-1 neutralization by antibody 2G12 entails reversible glycan binding that slows cell entry
Authors: Platt Emily J. , Gomes Michelle M. , Kabat David
Published: May 2012

Despite structural knowledge of broadly neutralizing monoclonal antibodies (NMAbs) complexed to HIV-1 gp120 and gp41 envelope glycoproteins, virus inactivation mechanisms have been difficult to prove, in part because neutralization assays are complex and were previously not understood. Concordant with recent evidence that HIV-1 titers are determined by a race between entry of cell-attached virions and competing inactivation processes, we show that NMAb 2G12, which binds to gp120 N-glycans with α (1, 2)-linked mannose termini and inhibits replication after passive transfer into patients, neutralizes by slowing entry of adsorbed virions. Accordingly, apparent neutralization is attenuated when a kinetically competing virus inactivation pathway is blocked. Moreover, removing 2G12 from media causes its dissociation from virions coupled to accelerated entry and restored infectivity, demonstrating the reversibility of neutralization. A difference between 2G12 dissociation and infectivity recovery rates implies that the inhibited complexes at virus–cell junctions contain several 2G12’s that must dissociate before entry commences. Quantitative microscopy of 2G12 binding and dissociation from single virions and studies using a split CCR5 coreceptor suggest that 2G12 competitively inhibits interactions between gp120’s V3 loop and the tyrosine sulfate-containing CCR5 amino terminus, thereby reducing assembly of complexes that catalyze entry. These results reveal a unique reversible kinetic mechanism for neutralization by an antibody that binds near a critical V3 region in the glycan shield of gp120.
Climate change impacts of US reactive nitrogen
Authors: Pinder Robert W. , Davidson Eric A. , Goodale Christine L. , Greaver Tara L. , Herrick Jeffrey D. , Liu Lingli
Published: May 2012

Fossil fuel combustion and fertilizer application in the United States have substantially altered the nitrogen cycle, with serious effects on climate change. The climate effects can be short-lived, by impacting the chemistry of the atmosphere, or long-lived, by altering ecosystem greenhouse gas fluxes. Here we develop a coherent framework for assessing the climate change impacts of US reactive nitrogen emissions, including oxides of nitrogen, ammonia, and nitrous oxide (N
2
O). We use the global temperature potential (GTP), calculated at 20 and 100 y, in units of CO
2
equivalents (CO
2
e), as a common metric. The largest cooling effects are due to combustion sources of oxides of nitrogen altering tropospheric ozone and methane concentrations and enhancing carbon sequestration in forests. The combined cooling effects are estimated at −290 to −510 Tg CO
2
e on a GTP
20
basis. However, these effects are largely short-lived. On a GTP
100
basis, combustion contributes just −16 to −95 Tg CO
2
e. Agriculture contributes to warming on both the 20-y and 100-y timescales, primarily through N
2
O emissions from soils. Under current conditions, these warming and cooling effects partially offset each other. However, recent trends show decreasing emissions from combustion sources. To prevent warming from US reactive nitrogen, reductions in agricultural N
2
O emissions are needed. Substantial progress toward this goal is possible using current technology. Without such actions, even greater CO
2
emission reductions will be required to avoid dangerous climate change.
Quantitative patterns of stylistic influence in the evolution of literature
Authors: Hughes James M. , Foti Nicholas J. , Krakauer David C. , Rockmore Daniel N.
Published: May 2012

Literature is a form of expression whose temporal structure, both in content and style, provides a historical record of the evolution of culture. In this work we take on a quantitative analysis of literary style and conduct the first large-scale temporal stylometric study of literature by using the vast holdings in the Project Gutenberg Digital Library corpus. We find temporal stylistic localization among authors through the analysis of the similarity structure in feature vectors derived from content-free word usage, nonhomogeneous decay rates of stylistic influence, and an accelerating rate of decay of influence among modern authors. Within a given time period we also find evidence for stylistic coherence with a given literary topic, such that writers in different fields adopt different literary styles. This study gives quantitative support to the notion of a literary “style of a time” with a strong trend toward increasingly contemporaneous stylistic influence.
Cytotoxic immunological synapses do not restrict the action of interferon-γ to antigenic target cells
Authors: Sanderson Nicholas Stephen Rennie , Puntel Mariana , Kroeger Kurt M. , Bondale Niyati S. , Swerdlow Mark , Iranmanesh Niloufar , Yagita Hideo , Ibrahim Ahmed , Castro Maria G. , Lowenstein Pedro R.
Published: May 2012

Following antigen recognition on target cells, effector T cells establish immunological synapses and secrete cytokines. It is thought that T cells secrete cytokines in one of two modes: either synaptically (i.e., toward antigenic target cells) or multidirectionally, affecting a wider population of cells. This paradigm predicts that synaptically secreted cytokines such as IFN-γ will preferentially signal to antigenic target cells contacted by the T cell through an immunological synapse. Despite its physiological significance, this prediction has never been tested. We developed a live-cell imaging system to compare the responses of target cells and nonantigenic bystanders to IFN-γ secreted by CD8+, antigen-specific, cytotoxic T cells. Both target cells and surrounding nontarget cells respond robustly. This pattern of response was detected even at minimal antigenic T-cell stimulation using low doses of antigenic peptide, or altered peptide ligands. Although cytotoxic immunological synapses restrict killing to antigenic target cells, the effects of IFN-γ are more widespread.
Irregular topography at the Earth’s inner core boundary
Authors: Dai Zhiyang , Wang Wei , Wen Lianxing
Published: May 2012

Compressional seismic wave reflected off the Earth’s inner core boundary (ICB) from earthquakes occurring in the Banda Sea and recorded at the Hi-net stations in Japan exhibits significant variations in travel time (from -2 to 2.5 s) and amplitude (with a factor of more than 4) across the seismic array. Such variations indicate that Earth’s ICB is irregular, with a combination of at least two scales of topography: a height variation of 14 km changing within a lateral distance of no more than 6 km, and a height variation of 4–8 km with a lateral length scale of 2–4 km. The characteristics of the ICB topography indicate that small-scale variations of temperature and/or core composition exist near the ICB, and/or the ICB topographic surface is being deformed by small-scale forces out of its thermocompositional equilibrium position and is metastable.
Greater India Basin hypothesis and a two-stage Cenozoic collision between India and Asia
Authors: van Hinsbergen Douwe J. J. , Lippert Peter C. , Dupont-Nivet Guillaume , McQuarrie Nadine , Doubrovine Pavel V. , Spakman Wim , Torsvik Trond H.
Published: May 2012

Cenozoic convergence between the Indian and Asian plates produced the archetypical continental collision zone comprising the Himalaya mountain belt and the Tibetan Plateau. How and where India–Asia convergence was accommodated after collision at or before 52 Ma remains a long-standing controversy. Since 52 Ma, the two plates have converged up to 3,600 ± 35 km, yet the upper crustal shortening documented from the geological record of Asia and the Himalaya is up to approximately 2,350-km less. Here we show that the discrepancy between the convergence and the shortening can be explained by subduction of highly extended continental and oceanic Indian lithosphere within the Himalaya between approximately 50 and 25 Ma. Paleomagnetic data show that this extended continental and oceanic “Greater India” promontory resulted from 2,675 ± 700 km of North–South extension between 120 and 70 Ma, accommodated between the Tibetan Himalaya and cratonic India. We suggest that the approximately 50 Ma “India”–Asia collision was a collision of a Tibetan-Himalayan microcontinent with Asia, followed by subduction of the largely oceanic Greater India Basin along a subduction zone at the location of the Greater Himalaya. The “hard” India–Asia collision with thicker and contiguous Indian continental lithosphere occurred around 25–20 Ma. This hard collision is coincident with far-field deformation in central Asia and rapid exhumation of Greater Himalaya crystalline rocks, and may be linked to intensification of the Asian monsoon system. This two-stage collision between India and Asia is also reflected in the deep mantle remnants of subduction imaged with seismic tomography.
Caenorhabditis elegans
POT-2 telomere protein represses a mode of alternative lengthening of telomeres with normal telomere lengths
Authors: Cheng Chen , Shtessel Ludmila , Brady Megan M. , Ahmed Shawn
Published: May 2012

Canonical telomere repeats at chromosome termini can be maintained by a telomerase-independent pathway termed alternative lengthening of telomeres (ALT). Human cancers that survive via ALT can exhibit long and heterogeneous telomeres, although many telomerase-negative tumors possess telomeres of normal length. Here, we report that
Caenorhabditis elegans
telomerase mutants that survived via ALT possessed either long or normal telomere lengths. Most ALT strains displayed end-to-end chromosome fusions, suggesting that critical telomere shortening occurred before or concomitant with ALT. ALT required the 9-1-1 DNA damage response complex and its clamp loader, HPR-17. Deficiency for the POT-2 telomere binding protein promoted ALT in telomerase mutants, overcame the requirement for the 9-1-1 complex in ALT, and promoted ALT with normal telomere lengths. We propose that telomerase-deficient human tumors with normal telomere lengths could represent a mode of ALT that is facilitated by telomere capping protein dysfunction.
Malignant hyperthermia susceptibility arising from altered resting coupling between the skeletal muscle L-type Ca
2+
channel and the type 1 ryanodine receptor
Authors: Eltit Jose Miguel , Bannister Roger A. , Moua Ong , Altamirano Francisco , Hopkins Philip M. , Pessah Isaac N. , Molinski Tadeusz F. , López Jose R. , Beam Kurt G. , Allen Paul D.
Published: May 2012

Malignant hyperthermia (MH) susceptibility is a dominantly inherited disorder in which volatile anesthetics trigger aberrant Ca
2+
release in skeletal muscle and a potentially fatal rise in perioperative body temperature. Mutations causing MH susceptibility have been identified in two proteins critical for excitation–contraction (EC) coupling, the type 1 ryanodine receptor (RyR1) and Ca
V
1.1, the principal subunit of the L-type Ca
2+
channel. All of the mutations that have been characterized previously augment EC coupling and/or increase the rate of L-type Ca
2+
entry. The Ca
V
1.1 mutation R174W associated with MH susceptibility occurs at the innermost basic residue of the IS4 voltage-sensing helix, a residue conserved among all Ca
V
channels [Carpenter D, et al. (2009)
BMC Med Genet
10:104–115.]. To define the functional consequences of this mutation, we expressed it in
dysgenic
(Ca
V
1.1 null) myotubes. Unlike previously described MH-linked mutations in Ca
V
1.1, R174W ablated the L-type current and had no effect on EC coupling. Nonetheless, R174W increased sensitivity of Ca
2+
release to caffeine (used for MH diagnostic in vitro testing) and to volatile anesthetics. Moreover, in Ca
V
1.1 R174W-expressing myotubes, resting myoplasmic Ca
2+
levels were elevated, and sarcoplasmic reticulum (SR) stores were partially depleted, compared with myotubes expressing wild-type Ca
V
1.1. Our results indicate that Ca
V
1.1 functions not only to activate RyR1 during EC coupling, but also to suppress resting RyR1-mediated Ca
2+
leak from the SR, and that perturbation of Ca
V
1.1 negative regulation of RyR1 leak identifies a unique mechanism that can sensitize muscle cells to MH triggers.
Mycobacterium tuberculosis
Eis protein initiates suppression of host immune responses by acetylation of DUSP16/MKP-7
Authors: Kim Kyoung Hoon , An Doo Ri , Song Jinsu , Yoon Ji Young , Kim Hyoun Sook , Yoon Hye Jin , Im Ha Na , Kim Jieun , Kim Do Jin , Lee Sang Jae , Kim Ki-Hye , Lee Hye-Mi , Kim Hie-Joon , Jo Eun-Kyeong , Lee Jae Young , Suh Se Won
Published: May 2012

The intracellular pathogen
Mycobacterium tuberculosis
(
Mtb
) causes tuberculosis. Enhanced intracellular survival (Eis) protein, secreted by
Mtb
, enhances survival of
Mycobacterium smegmatis
(
Msm
) in macrophages.
Mtb
Eis was shown to suppress host immune defenses by negatively modulating autophagy, inflammation, and cell death through JNK-dependent inhibition of reactive oxygen species (ROS) generation.
Mtb
Eis was recently demonstrated to contribute to drug resistance by acetylating multiple amines of aminoglycosides. However, the mechanism of enhanced intracellular survival by
Mtb
Eis remains unanswered. Therefore, we have characterized both
Mtb
and
Msm
Eis proteins biochemically and structurally. We have discovered that
Mtb
Eis is an efficient
N
ɛ
-acetyltransferase, rapidly acetylating Lys55 of dual-specificity protein phosphatase 16 (DUSP16)/mitogen-activated protein kinase phosphatase-7 (MKP-7), a JNK-specific phosphatase. In contrast,
Msm
Eis is more efficient as an
N
α
-acetyltransferase. We also show that
Msm
Eis acetylates aminoglycosides as readily as
Mtb
Eis. Furthermore,
Mtb
Eis, but not
Msm
Eis, inhibits LPS-induced JNK phosphorylation. This functional difference against DUSP16/MKP-7 can be understood by comparing the structures of two Eis proteins. The active site of
Mtb
Eis with a narrow channel seems more suitable for sequence-specific recognition of the protein substrate than the pocket-shaped active site of
Msm
Eis. We propose that
Mtb
Eis initiates the inhibition of JNK-dependent autophagy, phagosome maturation, and ROS generation by acetylating DUSP16/MKP-7. Our work thus provides insight into the mechanism of suppressing host immune responses and enhancing mycobacterial survival within macrophages by
Mtb
Eis.
Orthodenticle and Kruppel homolog 1 regulate
Drosophila
photoreceptor maturation
Authors: Fichelson Pierre , Brigui Amira , Pichaud Franck
Published: May 2012

Neurons present a wide variety of morphologies that are associated with their specialized functions. However, to date very few pathways and factors regulating neuronal maturation, including morphogenesis, have been identified. To address this issue we make use here of the genetically amenable developing fly photoreceptor (PR). Whereas this sensory neuron is specified early during retinal development, its maturation spans several days. During this time, this neuron acquires specialized membrane domains while undergoing extensive polarity remodeling. In this study, we identify a pathway in which the conserved homeobox protein Orthodenticle (Otd) acts together with the ecdysone receptor (EcR) to directly repress the expression of the transcription factor (TF)
Kruppel homolog 1
(
Kr-h1
). We demonstrate that this pathway is not required to promote neuronal specification but is crucial to regulate PR maturation. PR maturation includes the remodeling of the cell’s epithelial features and associated apical membrane morphogenesis. Furthermore, we show that hormonal control coordinates PR differentiation and morphogenesis with overall development. This study demonstrates that during PR differentiation, transient repression of
Kr-h1
represents a key step regulating neuronal maturation. Down-regulation of
Kr-h1
expression has been previously associated with instances of neuronal remodeling in the fly brain. We therefore conclude that repression of this transcription factor represents a key step, enabling remodeling and maturation in a wide variety of neurons.
Immature integration and segregation of emotion-related brain circuitry in young children
Authors: Qin Shaozheng , Young Christina B. , Supekar Kaustubh , Uddin Lucina Q. , Menon Vinod
Published: May 2012

The human brain undergoes protracted development, with dramatic changes in expression and regulation of emotion from childhood to adulthood. The amygdala is a brain structure that plays a pivotal role in emotion-related functions. Investigating developmental characteristics of the amygdala and associated functional circuits in children is important for understanding how emotion processing matures in the developing brain. The basolateral amygdala (BLA) and centromedial amygdala (CMA) are two major amygdalar nuclei that contribute to distinct functions via their unique pattern of interactions with cortical and subcortical regions. Almost nothing is currently known about the maturation of functional circuits associated with these amygdala nuclei in the developing brain. Using intrinsic connectivity analysis of functional magnetic resonance imaging data, we investigated developmental changes in functional connectivity of the BLA and CMA in twenty-four 7- to 9-y-old typically developing children compared with twenty-four 19- to 22-y-old healthy adults. Children showed significantly weaker intrinsic functional connectivity of the amygdala with subcortical, paralimbic, and limbic structures, polymodal association, and ventromedial prefrontal cortex. Importantly, target networks associated with the BLA and CMA exhibited greater overlap and weaker dissociation in children. In line with this finding, children showed greater intraamygdala connectivity between the BLA and CMA. Critically, these developmental differences were reproducibly identified in a second independent cohort of adults and children. Taken together, our findings point toward weak integration and segregation of amygdala circuits in young children. These immature patterns of amygdala connectivity have important implications for understanding typical and atypical development of emotion-related brain circuitry.
Archaeology as a social science
Authors: Smith Michael E. , Feinman Gary M. , Drennan Robert D. , Earle Timothy , Morris Ian
Published: May 2012

Because of advances in methods and theory, archaeology now addresses issues central to debates in the social sciences in a far more sophisticated manner than ever before. Coupled with methodological innovations, multiscalar archaeological studies around the world have produced a wealth of new data that provide a unique perspective on long-term changes in human societies, as they document variation in human behavior and institutions before the modern era. We illustrate these points with three examples: changes in human settlements, the roles of markets and states in deep history, and changes in standards of living. Alternative pathways toward complexity suggest how common processes may operate under contrasting ecologies, populations, and economic integration.
Historical effects on beta diversity and community assembly in Amazonian trees
Authors: Dexter Kyle G. , Terborgh John W. , Cunningham Clifford W.
Published: May 2012

We present a unique perspective on the role of historical processes in community assembly by synthesizing analyses of species turnover among communities with environmental data and independent, population genetic-derived estimates of among-community dispersal. We sampled floodplain and terra firme communities of the diverse tree genus
Inga
(Fabaceae) across a 250-km transect in Amazonian Peru and found patterns of distance-decay in compositional similarity in both habitat types. However, conventional analyses of distance-decay masked a zone of increased species turnover present in the middle of the transect. We estimated past seed dispersal among the same communities by examining geographic plastid DNA variation for eight widespread
Inga
species and uncovered a population genetic break in the majority of species that is geographically coincident with the zone of increased species turnover. Analyses of these and 12 additional
Inga
species shared between two communities located on opposite sides of the zone showed that the populations experienced divergence 42,000–612,000 y ago. Our results suggest that the observed distance decay is the result not of environmental gradients or dispersal limitation coupled with ecological drift—as conventionally interpreted under neutral ecological theory—but rather of secondary contact between historically separated communities. Thus, even at this small spatial scale, historical processes seem to significantly impact species’ distributions and community assembly. Other documented zones of increased species turnover found in the western Amazon basin or elsewhere may be related to similar historical processes.
Unexpected fold in the circumsporozoite protein target of malaria vaccines
Authors: Doud Michael B. , Koksal Adem C. , Mi Li-Zhi , Song Gaojie , Lu Chafen , Springer Timothy A.
Published: May 2012

Circumsporozoite (CS) protein is the major surface component ofPlasmodium falciparumsporozoites and is essential for host cell invasion. A vaccine containing tandem repeats, region III, and thrombospondin type-I repeat (TSR) of CS is efficacious in phase III trials but gives only a 35% reduction in severe malaria in the first year postimmunization. We solved crystal structures showing that region III and TSR fold into a single unit, an “αTSR” domain. The αTSR domain possesses a hydrophobic pocket and core, missing in TSR domains. CS binds heparin, but αTSR does not. Interestingly, polymorphic T-cell epitopes map to specialized αTSR regions. The N and C termini are unexpectedly close, providing clues for sporozoite sheath organization. Elucidation of a unique structure of a domain within CS enables rational design of next-generation subunit vaccines and functional and medicinal chemical investigation of the conserved hydrophobic pocket.
Cutaneous β-human papillomavirus E6 proteins bind Mastermind-like coactivators and repress Notch signaling
Authors: Tan Min Jie Alvin , White Elizabeth A. , Sowa Mathew E. , Harper J. Wade , Aster Jon C. , Howley Peter M.
Published: May 2012

The Notch signaling pathway is a key determinant in keratinocyte differentiation and growth cycle arrest, and has been reported to have a tumor suppressor function in skin. The papillomavirus life cycle is intricately linked to the differentiation status of keratinocytes. Papillomaviruses are associated with benign proliferative epithelial lesions in their respective hosts. Although human papillomaviruses (HPVs) associated with genital tract lesions have been extensively studied, studies of the cutaneous HPVs are more limited. In particular, it is well established that the E6 proteins of high-risk HPVs of the α-genus such as HPV16 and HPV18 mediate the degradation of p53 by its association with the ubiquitin ligase E6AP. In contrast, less is known about the cellular activities of the cutaneous HPVs of the β-genus. By using an unbiased proteomic approach, we identify MAML1 and other members of the Notch transcription complex as high-confidence cellular interacting proteins of E6 proteins of the β-genus HPVs and of the bovine papillomavirus type 1 associated with cutaneous fibropapillomas. We show that bovine papillomavirus type 1 and β-HPV E6 repress Notch transcriptional activation, and that this repression is dependent on an interaction with MAML1. Finally, we show that the expression levels of endogenous Notch target genes are repressed by β-HPV E6 proteins. These findings elucidate a mechanism of viral antagonism of Notch signaling, and suggest that Notch signaling is an important epithelial cell pathway target for the β-HPVs.
One influenza virus particle packages eight unique viral RNAs as shown by FISH analysis
Authors: Chou Yi-ying , Vafabakhsh Reza , Doğanay Sultan , Gao Qinshan , Ha Taekjip , Palese Peter
Published: May 2012

Influenza A virus possesses a segmented genome of eight negative-sense, single-stranded RNAs. The eight segments have been shown to be represented in approximately equal molar ratios in a virus population; however, the exact copy number of each viral RNA segment per individual virus particles has not been determined. We have established an experimental approach based on multicolor single-molecule fluorescent in situ hybridization (FISH) to study the composition of viral RNAs at single-virus particle resolution. Colocalization analysis showed that a high percentage of virus particles package all eight different segments of viral RNAs. To determine the copy number of each RNA segment within individual virus particles, we measured the photobleaching steps of individual virus particles hybridized with fluorescent probes targeting a specific viral RNA. By comparing the photobleaching profiles of probes against the HA RNA segment for the wild-type influenza A/Puerto Rico/8/34 (PR8) and a recombinant PR8 virus carrying two copies of the HA segment, we concluded that only one copy of HA segment is packaged into a wild type virus particle. Our results showed similar photobleaching behaviors for other RNA segments, suggesting that for the majority of the virus particles, only one copy of each RNA segment is packaged into one virus particle. Together, our results support that the packaging of influenza viral genome is a selective process.
Spreading the Risk: Native Trout Management in a Warmer and Less-Certain Future
Authors: Haak Amy L. , Williams Jack E.
Published: May 2012

Management strategies that increase biological diversity and promote varied approaches to population protection are more likely to succeed during a future in which global warming drives rapid environmental change and increases uncertainty of future conditions. We describe how the concept of a diverse management portfolio can be applied to native trout conservation by increasing representation (protecting and restoring diversity), resilience (having sufficiently large populations and intact habitats to facilitate recovery from rapid environmental change), and redundancy (saving a sufficient number of populations so that some can be lost without jeopardizing the species). Saving diversity for native trout requires the conservation of genetically pure populations, the protection and restoration of life history diversity, and the protection of populations across the historical range. Protecting larger stronghold populations is important because such populations will have a better chance of surviving future disturbances, including those associated with climate change. The long-term persistence of populations is likely to require management for larger population sizes and larger habitat patches than currently exist for many native trout populations. Redundancy among these elements is important given that many populations are small and occupy reduced habitat in fragmented stream systems and therefore are increasingly vulnerable to extirpation. Application of the concept is further described in case studies of Yellowstone cutthroat trout Oncorhynchus clarkii bouvieri and Rio Grande cutthroat trout O. clarkii virginalis, two subspecies that illustrate many of the challenges that are common to management of western native trout.

Received May 16, 2011; accepted January 12, 2012
B cell depletion therapy ameliorates autoimmune disease through ablation of IL-6–producing B cells
Authors: Barr Tom A. , Shen Ping , Brown Sheila , Lampropoulou Vicky , Roch Toralf , Lawrie Sarah , Fan Boli , O’Connor Richard A. , Anderton Stephen M. , Bar-Or Amit , Fillatreau Simon , Gray David
Published: May 2012

B cells have paradoxical roles in autoimmunity, exerting both pathogenic and protective effects. Pathogenesis may be antibody independent, as B cell depletion therapy (BCDT) leads to amelioration of disease irrespective of autoantibody ablation. However, the mechanisms of pathogenesis are poorly understood. We demonstrate that BCDT alleviates central nervous system autoimmunity through ablation of IL-6–secreting pathogenic B cells. B cells from mice with experimental autoimmune encephalomyelitis (EAE) secreted elevated levels of IL-6 compared with B cells from naive controls, and mice with a B cell–specific IL-6 deficiency showed less severe disease than mice with wild-type B cells. Moreover, BCDT ameliorated EAE only in mice with IL-6–sufficient B cells. This mechanism of pathogenesis may also operate in multiple sclerosis (MS) because B cells from MS patients produced more IL-6 than B cells from healthy controls, and this abnormality was normalized with B cell reconstitution after Rituximab treatment. This suggests that BCDT improved disease progression, at least partly, by eliminating IL-6–producing B cells in MS patients. Taking these data together, we conclude that IL-6 secretion is a major mechanism of B cell–driven pathogenesis in T cell–mediated autoimmune disease such as EAE and MS.
Regulation of intestinal inflammation by microbiota following allogeneic bone marrow transplantation
Authors: Jenq Robert R. , Ubeda Carles , Taur Ying , Menezes Clarissa C. , Khanin Raya , Dudakov Jarrod A. , Liu Chen , West Mallory L. , Singer Natalie V. , Equinda Michele J. , Gobourne Asia , Lipuma Lauren , Young Lauren F. , Smith Odette M. , Ghosh Arnab , Hanash Alan M. , Goldberg Jenna D. , Aoyama Kazutoshi , Blazar Bruce R. , Pamer Eric G. , R.M. van den Brink Marcel
Published: May 2012

Despite a growing understanding of the link between intestinal inflammation and resident gut microbes, longitudinal studies of human flora before initial onset of intestinal inflammation have not been reported. Here, we demonstrate in murine and human recipients of allogeneic bone marrow transplantation (BMT) that intestinal inflammation secondary to graft-versus-host disease (GVHD) is associated with major shifts in the composition of the intestinal microbiota. The microbiota, in turn, can modulate the severity of intestinal inflammation. In mouse models of GVHD, we observed loss of overall diversity and expansion of Lactobacillales and loss of Clostridiales. Eliminating Lactobacillales from the flora of mice before BMT aggravated GVHD, whereas reintroducing the predominant species of Lactobacillus mediated significant protection against GVHD. We then characterized gut flora of patients during onset of intestinal inflammation caused by GVHD and found patterns mirroring those in mice. We also identified increased microbial chaos early after allogeneic BMT as a potential risk factor for subsequent GVHD. Together, these data demonstrate regulation of flora by intestinal inflammation and suggest that flora manipulation may reduce intestinal inflammation and improve outcomes for allogeneic BMT recipients.
Ozone production rate as a function of electric field strength in oxygen
Authors: Aints Märt , Valk Fred , Plank Toomas , Paris Peeter , Jõgi Indrek
Published: May 2012

The ozone production rate in a dc low-current non-self-sustained discharge (dark discharge) in oxygen is measured systematically as a function of gas pressure and electric field strength in the range of reduced field strengths E/N = 120–800 Td and pressures p = 7–160 kPa. The fraction of energy consumed by electrons in the dark discharge is calculated and the ozone generation efficiency (the maximal energetic yield of ozone in an idealized discharge with negligible ion losses) is estimated. The reaction rate coefficient for oxygen dissociation by electron impact, deduced from the efficiency curve, is proposed.
Influence of the deposition method on interdiffusion of Ni/Ag bilayer thin films
Authors: Mashaiekhy J , Shafieizadeh Z , Nahidi H , Sharifi S
Published: May 2012

In this study, it has been shown that the dependence of interdiffusion phenomena in metallic thin films is largely related to the deposition method. Films were prepared by evaporation and unbalanced magnetron sputtering onto glass substrates. Rutherford backscattering spectrometry was used for quantitative compositional analysis of thin films, determination of structures and observation of interdiffusion in bilayer Ni/Ag films. The structures of the films were monitored by x-ray diffraction. The experimental results confirm that evaporated films are in a state of tensile stress, which increases the vacancy concentration and diffusion, whereas sputtered films are under compressive stress, which decreases the vacancy concentration, thus preventing diffusion.
Three-point bounds for energy minimization
Authors: Cohn Henry , Woo Jeechul
Published: May 2012

Three-point semidefinite programming bounds are one of the most powerful known tools for bounding the size of spherical codes. In this paper, we use them to prove lower bounds for the potential energy of particles interacting via a pair potential function. We show that our bounds are sharp for seven points in

R

P

2

\mathbb {R}\mathbb {P}^2

. Specifically, we prove that the seven lines connecting opposite vertices of a cube and of its dual octahedron are universally optimal. (In other words, among all configurations of seven lines through the origin, this one minimizes energy for all potential functions that are completely monotonic functions of squared chordal distance.) This configuration is the only known universal optimum that is not distance regular, and the last remaining universal optimum in

R

P

2

\mathbb {R}\mathbb {P}^2

. We also give a new derivation of semidefinite programming bounds and present several surprising conjectures about them.
Use of implantable cardioverter defibrillators in patients with left ventricular assist devices
Authors: Pettit Stephen J. , Petrie Mark C. , Connelly Derek T. , Japp Alan G. , Payne John R. , Haj‐Yahia Saleem , Gardner Roy S.
Published: May 2012

Patients with left ventricular assist devices (LVADs) are at high risk of sustained ventricular arrhythmias, but these may be remarkably well tolerated and the association with sudden death is unclear. Many patients who receive an LVAD already have an implantable cardioverter defibrillator (ICD). While it is standard practice to reactivate a previously implanted ICD in an LVAD recipient, this should include discussion of the revised risks and benefits of ICD therapy following LVAD implantation. In particular, patients should be warned that they might receive a significant number of ICD shocks that may not be life saving. When ICDs are reactivated, device programming should minimize the risk of repeated shocks for non‐sustained or well‐tolerated ventricular arrhythmias. Implantation of a primary prevention ICD after implantation of an LVAD is not supported by current evidence, poses potential risks, and should be the subject of a clinical trial before it becomes standard practice.
Autologous Transplantation of Peripheral Blood-derived Circulating Endothelial Progenitor Cells Attenuates Endotoxin-induced Acute Lung Injury in Rabbits by Direct Endothelial Repair and Indirect Immunomodulation
Authors: Cao Jian-Ping , He Xing-Ying , Xu Hai-Tao , Zou Zui , Shi Xue-Yin
Published: May 2012

Background

Studies have demonstrated the role of circulating endothelial progenitor cells (EPCs) in maintaining normal endothelial function and in endothelial repairing. This study was aimed to observe the protective effects of autologous transplantation of circulating EPCs against endotoxin-induced acute lung injury in rabbits and to investigate the underlying mechanisms.

Methods

One-hundred-and-fifty rabbits were enrolled. After acute lung injury was induced by endotoxin, autologous circulating EPCs, endothelial cell, or normal saline were transfused intravenously, respectively. Pao(2)/FiO(2) ratios, concentrations of plasma nitric oxide, malonyldialdehyde, and activity of superoxide dismutase were examined. The lung wet-to-dry weight ratios were counted; polymorphonuclear cell ratios and areas of hyaline membrane formation and hemorrhage were measured. The levels of interleukin-1β, E-selectin, intercellular adhesion molecule-1, interleukin-10, vascular endothelial growth factor protein, and inducible nitric oxide synthase protein were analyzed.

Results

Pao(2)/FiO(2) ratios were significantly increased with EPC transfusion. Infiltration of polymorphonuclear cells, lung wet-to-dry weight ratios, and area of hyaline membrane and hemorrhage in lung tissue were significantly decreased after EPC transplantation. Plasma level of nitric oxide and malondialdehyde were significantly inhibited, and the activity of superoxide dismutase was enhanced in the EPC-treated animals. EPC transplantation significantly increased level of interleukin-10 and vascular endothelial growth factor protein and reduced levels of interleukin-1β, E-selectin, intercellular adhesion molecule-1, and inducible nitric oxide synthase in injury lung tissues.

Conclusions

Autologous transplantation of circulating EPCs can partly restore the pulmonary endothelial function and effectively attenuate endotoxin-induced acute lung injury by direct endothelial repair and indirect immunomodulation of antioxidation and antiinflammation.
Hospital Stay and Mortality Are Increased in Patients Having a “Triple Low” of Low Blood Pressure, Low Bispectral Index, and Low Minimum Alveolar Concentration of Volatile Anesthesia
Authors: Sessler Daniel I. , Sigl Jeffrey C. , Kelley Scott D. , Chamoun Nassib G. , Manberg Paul J. , Saager Leif , Kurz Andrea , Greenwald Scott
Published: May 2012

Background

Low mean arterial pressure (MAP) and deep hypnosis have been associated with complications and mortality. The normal response to high minimum alveolar concentration (MAC) fraction of anesthetics is hypotension and low Bispectral Index (BIS) scores. Low MAP and/or BIS at lower MAC fractions may represent anesthetic sensitivity. The authors sought to characterize the effect of the triple low state (low MAP and low BIS during a low MAC fraction) on duration of hospitalization and 30-day all-cause mortality.

Methods

Mean intraoperative MAP, BIS, and MAC were determined for 24,120 noncardiac surgery patients at the Cleveland Clinic, Cleveland, Ohio. The hazard ratios associated with combinations of MAP, BIS, and MAC values greater or less than a reference value were determined. The authors also evaluated the association between cumulative triple low minutes, and excess length-of-stay and 30-day mortality.

Results

Means (±SD) defining the reference, low, and high states were 87 ± 5 mmHg (MAP), 46 ± 4 (BIS), and 0.56 ± 0.11 (MAC). Triple lows were associated with prolonged length of stay (hazard ratio 1.5, 95% CI 1.3-1.7). Thirty-day mortality was doubled in double low combinations and quadrupled in the triple low group. Triple low duration ≥60 min quadrupled 30-day mortality compared with ≤15 min. Excess length of stay increased progressively from ≤15 min to ≥60 min of triple low.

Conclusions

The occurrence of low MAP during low MAC fraction was a strong and highly significant predictor for mortality. When these occurrences were combined with low BIS, mortality risk was even greater. The values defining the triple low state were well within the range that many anesthesiologists tolerate routinely.
Sugammadex Ideal Body Weight Dose Adjusted by Level of Neuromuscular Blockade in Laparoscopic Bariatric Surgery
Authors: Llauradó Sandra , Sabaté Antoni , Ferreres Eva , Camprubí Inmaculada , Cabrera Anna
Published: May 2012

Background

Bariatric surgery patients are at risk of perioperative airway collapse. Neuromuscular blockade should be fully reversed before tracheal extubation. The optimal dosage of the reversal agent sugammadex in the morbidly obese is still unknown. This study explored the sugammadex dose adjusted according to train-of-four ratio (TOFR).

Methods

Prospective observational study of consecutive patients scheduled for laparoscopic bariatric surgery. To reverse a deep blockade (2 or fewer posttetanic twitches), a dose of sugammadex of 4 mg/kg ideal body weight (IBW) was followed by a second dose of 2 mg/kg IBW if the TOFR was less than 0.9 after 3 min. To reverse a moderate blockade (reappearance of the second twitch in the TOF), a 2 mg/kg IBW dose of sugammadex was followed by a second dose of 2 mg/kg IBW if the TOFR was less than 0.9 after 2 min. Sugammadex effectiveness was reflected by the time required to obtain a TOFr of 0.9 or more.

Results

A total of 120 patients were included. The blockade was deep at the end of surgery in 43 and moderate in 77. The median times (range) to TOFR of 0.9 or more were 167 (20-460) seconds and 113 (28-300) seconds in deep and moderate blockades, respectively (P < 0.05). The percentage of patients requiring a second dose of sugammadex were larger after deep blockades (39.5% [n = 17] vs. 23.4% [n = 18] after moderate blockades); the difference was not significant.

Conclusion

A sugammadex dose calculated according to IBW is insufficient for reversing both deep and moderate blockades in morbidly obese patients.