bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Prostaglandin E1on the Preparation of Platelet Concentrates in Dogs
Authors: Segawa K. , Kondo T. , Kimura S. , Fujimoto A. , Kato T. , Ishikawa T. , Neo S. , Hisasue M. , Yamada T. , Tsuchiya R.
Published: January 2012

Background

Platelet concentrates (PC) are prepared by centrifugation of platelet‐rich plasma (PRP) that is prepared by centrifugation of whole blood. The resuspension of the platelet pellet duringPCpreparation from dogs is difficult because of platelet activation induced by centrifugation.

Objectives

To investigate the efficacy of adding prostaglandin E1(PGE1) to prevent platelet activation duringPCpreparation from dogs.

Animals

Fifteen healthy Beagle dogs.

Methods

Prospective, experimental trial:PGE1was added toPRPbefore the high‐speed centrifugation duringPCpreparation. To estimate the effect of this addition, we assessed the platelet aggregability before transfusion, the survival of the platelets after transfusion, and the platelet reactivity after transfusion, which is estimated by the P‐selectin expression of the platelets when stimulated by thrombin.

Results

The difficulty associated with platelet resuspension was resolved byPGE1.PGE1strongly inhibited platelet aggregation induced by collagen andADP; however, it recovered after the platelets were resuspended in plasma withoutPGE1(mean aggregation ratio; collagen: 10.00–80.80%,ADP: 8.20–53.60%). Survival of the platelets after transfusion was not affected byPGE1(mean 8.04 and 7.56 days, without and withPGE1), and thrombin‐induced P‐selectin expression after transfusion inPGE1‐treatedPCwas also well maintained (mean positive ratio 53.7 and 47.9%, before and 24 hours after transfusion).

Conclusions and Clinical Importance

The addition ofPGE1inPRPbefore the centrifugation ofPRPcan improve the preparation efficiency ofPCfrom dogs, while maintaining the therapeutic efficacy of the platelets.
Grief Experiences and Expectance of Suicide
Authors: Wojtkowiak Joanna , Wild Verena , Egger Jos
Published: January 2012

Suicide is generally viewed as an unexpected cause of death. However, some suicides might be expected to a certain extent, which needs to be further studied. The relationships between expecting suicide, feeling understanding for the suicide, and later grief experiences were explored. In total, 142 bereaved participants completed the Grief Experience Questionnaire and additional measurements on expectance and understanding. Results supported the prediction of a link between expecting suicide and understanding the suicide. Higher expectance and understanding were related to less searching for explanation and preoccupation with the suicide. There was no direct association with other grief experiences. We conclude that more attention should be brought to the relation between expecting the suicide of a loved one and later grief responses in research and in clinical practice.
Giving cognition a helping hand: The effect of congruent gestures on object name retrieval
Authors: Pine Karen J. , Reeves Lindsey , Howlett Neil , Fletcher Ben (C)
Published: January 2012

The gestures that accompany speech are more than just arbitrary hand movements or communicative devices. They are simulated actions that can both prime and facilitate speech and cognition. This study measured participants’ reaction times for naming degraded images of objects when simultaneously adopting a gesture that was either congruent with the target object, incongruent with it, and when not making any hand gesture. A within‐subjects design was used, with participants (N= 122) naming 10 objects under each condition. Participants named the objects significantly faster when adopting a congruent gesture than when not gesturing at all. Adopting an incongruent gesture resulted in significantly slower naming times. The findings are discussed in the context of the intrapersonal cognitive and facilitatory effects of gestures and underline the relatedness between language, action, and cognition.
FEBio: Finite Elements for Biomechanics
Authors: Maas Steve A. , Ellis Benjamin J. , Ateshian Gerard A. , Weiss Jeffrey A.
Published: January 2012

In the field of computational biomechanics, investigators have primarily used commercial software that is neither geared toward biological applications nor sufficiently flexible to follow the latest developments in the field. This lack of a tailored software environment has hampered research progress, as well as dissemination of models and results. To address these issues, we developed the FEBio software suite (http://mrl.sci.utah.edu/software/febio), a nonlinear implicit finite element (FE) framework, designed specifically for analysis in computational solid biomechanics. This paper provides an overview of the theoretical basis of FEBio and its main features. FEBio offers modeling scenarios, constitutive models, and boundary conditions, which are relevant to numerous applications in biomechanics. The open-source FEBio software is written in C++, with particular attention to scalar and parallel performance on modern computer architectures. Software verification is a large part of the development and maintenance of FEBio, and to demonstrate the general approach, the description and results of several problems from the FEBio Verification Suite are presented and compared to analytical solutions or results from other established and verified FE codes. An additional simulation is described that illustrates the application of FEBio to a research problem in biomechanics. Together with the pre- and postprocessing software PREVIEW and POSTVIEW, FEBio provides a tailored solution for research and development in computational biomechanics.
A Semi-Empirical Cell Dynamics Model for Bone Turnover Under External Stimulus
Authors: Carew E. Owen
Published: January 2012

The normal periodic turnover of bone is referred to as remodeling. In remodeling, old or damaged bone is removed during a ‘resorption’ phase and new bone is formed in its place during a ‘formation’ phase in a sequence of events known as coupling. Resorption is preceded by an ‘activation’ phase in which the signal to remodel is initiated and transmitted. Remodeling is known to involve the interaction of external stimuli, bone cells, calcium and phosphate ions, and several proteins, hormones, molecules, and factors. In this study, a semi-empirical cell dynamics model for bone remodeling under external stimulus that accounts for the interaction between bone mass, bone fluid calcium, bone calcium, and all three major bone cell types, is presented. The model is formulated to mimic biological coupling by solving separately and sequentially systems of ODEs for the activation, resorption, and formation phases of bone remodeling. The charateristic time for resorption (20 days) and the amount of resorption (∼0.5%) are fixed for all simulations, but the formation time at turnover is an output of the model. The model was used to investigate the effects of different types of strain stimuli on bone turnover under bone fluid calcium balance and imbalance conditions. For bone fluid calcium balance, the model predicts complete turnover after 130 days of formation under constant 1000 microstrain stimulus; after 47 days of formation under constant 2000 microstrain stimulus; after 173 days of formation under strain-free conditions, and after 80 days of formation under monotonic increasing strain stimulus from 1000 to 2000 microstrain. For bone fluid calcium imbalance, the model predicts that complete turnover occurs after 261 days of formation under constant 1000 microstrain stimulus and that turnover never occurs under strain-free conditions. These predictions were not impacted by mean dynamic input strain stimuli of 1000 and 2000 microstrain at 1 Hz and 1000 microstrain amplitude. The formation phase of remodeling lasts longer than the resorption phase, increased strain stimulus accelerates bone turnover, while absence of strain significantly delays or prevents it, and formation time for turnover under monotonic increasing strain conditions is intermediate to those for constant strain stimuli at the minimum and maximum monotonic strain levels. These results are consistent with the biology, and with Frost’s mechanostat theory.
Electrical properties of C60 and Si codoped GaAs layers
Authors: Nishinaga Jiro , Horikoshi Yoshiji
Published: January 2012

C60 uniformly doped GaAs and C60, Si codoped GaAs layers are grown by a migration enhanced epitaxy method. C60 doped GaAs layers show a single and sharp diffraction peak in x-ray diffraction and only an LO phonon peak is confirmed, indicating that the crystalline quality is fairly good. All of the C60 doped GaAs layers have highly resistive characteristics, and C60, Si codoped GaAs layers show n-type conductivity only when the Si concentration is of the same order or greater than the total carbon concentrations. At low temperatures the conductivity of the C60, Si codoped GaAs layers increases with exposure to light whose energy is below the GaAs bandgap energy. The electron concentrations and mobilities of the layers are confirmed to be increased under illumination by wavelengths between 900 and 1100 nm. These results imply that the electron transitions from the valence band to the trap levels and from the trap levels to the conduction band occur simultaneously as if the traps act as intralevels. As a result, the carrier concentrations are enhanced in the same way they would be if the excitation was above the GaAs bandgap energy.
Genome Sequence of the Marine Bacterium Vibrio campbellii DS40M4, Isolated from Open Ocean Water
Authors: Dias Graciela M. , Thompson Cristiane C. , Fishman Brian , Naka Hiroaki , Haygood Margo G. , Crosa Jorge H. , Thompson Fabiano L.
Published: January 2012

Vibrio
sp. strain DS40M4 is a marine bacterium that was isolated from open ocean water. In this work, using genomic taxonomy, we were able to classify this bacterium as
V. campbellii
. Our genomic analysis revealed that
V. campbellii
DS40M4 harbors genes related to iron transport, virulence, and environmental fitness, such as those encoding anguibactin and vanchrobactin biosynthesis proteins, type II, III, IV, and VI secretion systems, and proteorhodopsin.
Life and Death of Deep-Sea Vents: Bacterial Diversity and Ecosystem Succession on Inactive Hydrothermal Sulfides
Authors: Sylvan Jason B. , Toner Brandy M. , Edwards Katrina J.
Published: January 2012

Hydrothermal chimneys are a globally dispersed habitat on the seafloor associated with mid-ocean ridge (MOR) spreading centers. Active, hot, venting sulfide structures from MORs have been examined for microbial diversity and ecology since their discovery in the mid-1970s, and recent work has also begun to explore the microbiology of inactive sulfides—structures that persist for decades to millennia and form moderate to massive deposits at and below the seafloor. Here we used tag pyrosequencing of the V6 region of the 16S rRNA and full-length 16S rRNA sequencing on inactive hydrothermal sulfide chimney samples from 9°N on the East Pacific Rise to learn their bacterial composition, metabolic potential, and succession from venting to nonventing (inactive) regimes. Alpha-, beta-, delta-, and gammaproteobacteria and members of the phylum
Bacteroidetes
dominate all inactive sulfides. Greater than 26% of the V6 tags obtained are closely related to lineages involved in sulfur, nitrogen, iron, and methane cycling. Epsilonproteobacteria represent <4% of the V6 tags recovered from inactive sulfides and 15% of the full-length clones, despite their high abundance in active chimneys. Members of the phylum
Aquificae
, which are common in active vents, were absent from both the V6 tags and full-length 16S rRNA data sets. In both analyses, the proportions of alphaproteobacteria, betaproteobacteria, and members of the phylum
Bacteroidetes
were greater than those found on active hydrothermal sulfides. These shifts in bacterial population structure on inactive chimneys reveal ecological succession following cessation of venting and also imply a potential shift in microbial activity and metabolic guilds on hydrothermal sulfides, the dominant biome that results from seafloor venting.

IMPORTANCE
Hydrothermal chimneys are globally dispersed seafloor habitats associated with mid-ocean ridge spreading centers. Active, hot, venting chimneys have been examined for microbial ecology since their discovery in the late 1970s, but the microbiology of inactive chimneys, which may persist for thousands of years, has only recently been explored. We studied bacterial diversity on inactive hydrothermal sulfide chimney samples from 9°N on the East Pacific Rise to learn their bacterial community composition, potential ecological roles, and succession from active venting to inactive chimneys. Many bacteria on inactive sulfide chimneys are closely related to lineages involved in sulfur, nitrogen, iron, and methane cycling, and two common groups found on active chimneys are nearly absent from inactive vents, where they were replaced by groups likely involved in the elemental cycling mentioned above. Our findings reveal that ecological succession occurs on hydrothermal sulfides after active venting ceases and also imply a potential shift in microbial metabolic guilds.
A cellular factor stimulates ligand-dependent release of hsp90 from the basic helix-loop-helix dioxin receptor.
Authors: McGuire J , Whitelaw M L , Pongratz I , Gustafsson J A , Poellinger L
Published: January 2012

In response to dioxin, the nuclear basic helix-loop-helix (bHLH) dioxin receptor forms a complex with the bHLH partner factor Arnt that regulates target gene transcription by binding to dioxin-responsive sequence motifs. Previously, we have demonstrated that the latent form of dioxin receptor present in extracts from untreated cells is stably associated with molecular chaperone protein hsp90, and Arnt is not a component of this complex. Here, we used a coimmunoprecipitation assay to demonstrate that the in vitro-translated dioxin receptor, but not Arnt, is stably associated with hsp90. Although it showed ligand-binding activity, the in vitro-translated dioxin receptor failed to dissociate from hsp90 upon exposure to ligand. Addition of a specific fraction from wild-type hepatoma cells, however, to the in vitro-expressed receptor promoted dioxin-dependent release of hsp90. This stimulatory effect was mediated via the bHLH dimerization and DNA-binding motif of the receptor. Moreover, ligand-dependent release of hsp90 from the receptor was not promoted by fractionated cytosolic extracts from mutant hepatoma cells which are deficient in the function of bHLH dioxin receptor partner factor Arnt. Thus, our results provide a novel model for regulation of bHLH factor activity and suggest that derepression of the dioxin receptor by ligand-induced release of hsp90 may require bHLH-mediated concomitant recruitment of an additional cellular factor, possibly the structurally related bHLH dimerization partner factor Arnt. In support of this model, addition of in vitro-expressed wild-type Arnt, but not a mutated form of Arnt lacking the bHLH motif, promoted release of hsp90 from the dioxin receptor in the presence of dioxin.
The interaction of small domains between the subunits of phosphatidylinositol 3-kinase determines enzyme activity.
Authors: Klippel A , Escobedo J A , Hirano M , Williams L T
Published: January 2012

Previous studies have suggested that the two subunits of phosphatidylinositol (PI) 3-kinase, p85 and p110, function as localizing and catalytic subunits, respectively. Using recombinant p85 and p110 molecules, we have reconstituted the specific interaction between the two subunits of mouse PI 3-kinase in cells and in vitro. We have previously shown that the region between the two Src homology 2 (SH2) domains of p85 is able to form a functional complex with the 110-kDa subunit in vivo. In this report, we identify the corresponding domain in p110 which directs the binding to p85. We demonstrate that the interactive domains in p85 and p110 are less than 103 and 124 amino acids, respectively, in size. We also show that the association of p85 and p110 mediated by these domains is critical for PI 3-kinase activity. Surprisingly, a complex between a 102-amino-acid segment of p85 and the full-length p110 molecule is catalytically active, whereas p110 alone has no activity. In addition to the catalytic domain in the carboxy-terminal region, 123 amino acids at the amino terminus of p110 were required for catalytic activity and were sufficient for the interaction with p85. These results indicate that the 85-kDa subunit, previously thought to have only a linking role in localizing the p110 catalytic subunit, is an important component of the catalytic complex.
Radiation therapy in malignant spinal cord compression: what is the current knowledge on fractionation schedules? A systematic literature review
Authors: Løhre Erik Torbjørn , Lund Jo-Åsmund , Kaasa Stein
Published: January 2012

Malignant spinal cord compression (MSCC) in patients with short life expectancy is most frequently treated with radiotherapy and/or corticosteroids. Hypofractionation has been proven to be efficient in metastatic bone pain, but the level of evidence for hypofractionation in MSCC is limited. Searches were performed in PubMed, Embase and the Cochrane Library for all relevant articles. Two randomised controlled trials (RCTs) were identified. The first RCT compared hypofractionation (8 gray (Gy)×2) with a more fractionated regimen. No differences in symptom control, duration of response or survival were detected. The second RCT compared 8 Gy×2 with 8 Gy×1. No significant differences in symptom control, duration of response or survival were detected. Five prospective non-randomised studies identified no differences in post-treatment motor function. Of 17 identified retrospective studies the largest included 1304 patients, treated with five different regimens ranging from 8 Gy×1 to 2 Gy×20, and found similar post-treatment ambulatory status. A Cochrane review based on the first published RCT concluded that short courses of radiotherapy appear to be justified in patients with a poor prognosis.
Brain temperature changes during selective cooling with endovascular intracarotid cold saline infusion: simulation using human data fitted with an integrated mathematical model
Authors: Neimark Matthew Aaron Harold , Konstas Angelos Aristeidis , Lee Leslie , Laine Andrew Francis , Pile-Spellman John , Choi Jae
Published: January 2012

The feasibility of rapid cerebral hypothermia induction in humans with intracarotid cold saline infusion (ICSI) was investigated using a hybrid approach of jugular venous bulb temperature (JVBT) sampling and mathematical modeling of transient and steady state brain temperature distribution. This study utilized both forward mathematical modeling, in which brain temperatures were predicted based on input saline temperatures, and inverse modeling, where brain temperatures were inferred based on JVBT. Changes in ipsilateral anterior circulation territory temperature (IACT) were estimated in eight patients as a result of 10 min of a cold saline infusion of 33 ml/min. During ICSI, the measured JVBT dropped by 0.76±0.18°C while the modeled JVBT decreased by 0.86±0.18°C. The modeled IACT decreased by 2.1±0.23°C. In the inverse model, IACT decreased by 1.9±0.23°C. The results of this study suggest that mild cerebral hypothermia can be induced rapidly and safely with ICSI in the neuroangiographical setting. The JVBT corrected mathematical model can be used as a non-invasive estimate of transient and steady state cerebral temperature changes.
Cache-Oblivious Algorithms
Authors: Frigo Matteo , Leiserson Charles E. , Prokop Harald , Ramachandran Sridhar
Published: January 2012

This article presents asymptotically optimal algorithms for rectangular matrix transpose, fast Fourier transform (FFT), and sorting on computers with multiple levels of caching. Unlike previous optimal algorithms, these algorithms are
cache oblivious
: no variables dependent on hardware parameters, such as cache size and cache-line length, need to be tuned to achieve optimality. Nevertheless, these algorithms use an optimal amount of work and move data optimally among multiple levels of cache. For a cache with size
M
and cache-line length
B
where
M
=
Ω
(
B
2
), the number of cache misses for an
m
×
n
matrix transpose is
Θ
(1 +
mn
/
B
). The number of cache misses for either an
n
-point FFT or the sorting of
n
numbers is
Θ
(1 + (
n
/
B
)(1 + log
M n
)). We also give a
Θ
(
mnp
)-work algorithm to multiply an
m
×
n
matrix by an
n
×
p
matrix that incurs
Θ
(1 + (
mn
+
np
+
mp
)/
B
+
mnp
/
B
√
M
) cache faults.

We introduce an “ideal-cache” model to analyze our algorithms. We prove that an optimal cache-oblivious algorithm designed for two levels of memory is also optimal for multiple levels and that the assumption of optimal replacement in the ideal-cache model can be simulated efficiently by LRU replacement. We offer empirical evidence that cache-oblivious algorithms perform well in practice.
DAPSCO
Authors: García-Guirado Antonio , Fernández-Pascual Ricardo , Ros Alberto , García José M.
Published: January 2012

Many-core tiled CMP proposals often assume a partially shared last level cache (LLC) since this provides a good compromise between access latency and cache utilization. In this paper, we propose a novel way to map memory addresses to LLC banks that takes into account the average distance between the banks and the tiles that access them. Contrary to traditional approaches, our mapping does not group the tiles in clusters within which all the cores access the same bank for the same addresses. Instead, two neighboring cores access different sets of banks minimizing the average distance travelled by the cache requests. Results for a 64-core CMP show that our proposal improves both execution time and the energy consumed by the network by 13% when compared to a traditional mapping. Moreover, our proposal comes at a negligible cost in terms of hardware and its benefits in both energy and execution time increase with the number of cores.
FlexSig
Authors: Orosa Lois , Antelo Elisardo , Bruguera Javier D.
Published: January 2012

With the advent of chip multiprocessors, new techniques have been developed to make parallel programing easier and more reliable. New parallel programing paradigms and new methods of making the execution of programs more efficient and more reliable have been developed. Usually, these improvements require hardware support to avoid a system slowdown.

Signatures based on Bloom filters are widely used as hardware support for parallel programing in chip multiprocessors. Signatures are used in Transactional Memory, thread-level speculation, parallel debugging, deterministic replay and other tools and applications. The main limitation of hardware signatures is the lack of flexibility: if signatures are designed with a given configuration, tailored to the requirements of a specific tool or application, it is likely that they do not fit well for other different requirements.

In this paper a new hardware signature organization, called
Flexible Signatures
(
FlexSig
), is proposed.
FlexSig
can change dynamically the resources assigned to a given signature and the number of signatures in the system, by redistributing the available hardware resources according to the system requirements. This allows higher flexibility than with traditional fixed-resources signatures based on Bloom filters, while maintaining a low false positive rate.

FlexSig
has been evaluated by comparing it with signatures based on parallel Bloom filters, and we conclude that
FlexSig
outperforms (in terms of false positive rate) conventional parallel Bloom filters in most cases, due to its ability to use all the signature resources available.
The accelerator store
Authors: Lyons Michael J. , Hempstead Mark , Wei Gu-Yeon , Brooks David
Published: January 2012

This paper presents the many-accelerator architecture, a design approach combining the scalability of homogeneous multi-core architectures and system-on-chip's high performance and power-efficient hardware accelerators. In preparation for systems containing tens or hundreds of accelerators, we characterize a diverse pool of accelerators and find each contains significant amounts of SRAM memory (up to 90% of their area). We take advantage of this discovery and introduce the accelerator store, a scalable architectural component to minimize accelerator area by sharing its memories between accelerators. We evaluate the accelerator store for two applications and find significant system area reductions (30%) in exchange for small overheads (2% performance, 0%--8% energy). The paper also identifies new research directions enabled by the accelerator store and the many-accelerator architecture.
TRPM2 Ca2+ channel regulates energy balance and glucose metabolism
Authors: Zhang Zhiyou , Zhang Wenyi , Jung Dae Young , Ko Hwi Jin , Lee Yongjin , Friedline Randall H. , Lee Eunjung , Jun John , Ma Zhexi , Kim Francis , Tsitsilianos Nicholas , Chapman Kathryn , Morrison Alastair , Cooper Marcus P. , Miller Barbara A. , Kim Jason K.
Published: January 2012

TRPM2 Ca2+-permeable cation channel is widely expressed and activated by markers of cellular stress. Since inflammation and stress play a major role in insulin resistance, we examined the role of TRPM2 Ca2+ channel in glucose metabolism. A 2-h hyperinsulinemic euglycemic clamp was performed in TRPM2-deficient (KO) and wild-type mice to assess insulin sensitivity. To examine the effects of diet-induced obesity, mice were fed a high-fat diet for 4–10 mo, and metabolic cage and clamp studies were conducted in conscious mice. TRPM2-KO mice were more insulin sensitive partly because of increased glucose metabolism in peripheral organs. After 4 mo of high-fat feeding, TRPM2-KO mice were resistant to diet-induced obesity, and this was associated with increased energy expenditure and elevated expressions of PGC-1α, PGC-1β, PPARα, ERRα, TFAM, and MCAD in white adipose tissue. Hyperinsulinemic euglycemic clamps showed that TRPM2-KO mice were more insulin sensitive, with increased Akt and GSK-3β phosphorylation in heart. Obesity-mediated inflammation in adipose tissue and liver was attenuated in TRPM2-KO mice. Overall, TRPM2 deletion protected mice from developing diet-induced obesity and insulin resistance. Our findings identify a novel role of TRPM2 Ca2+ channel in the regulation of energy expenditure, inflammation, and insulin resistance.
The calcium-sensing receptor complements parathyroid hormone-induced bone turnover in discrete skeletal compartments in mice
Authors: Xue Yingben , Xiao Yongjun , Liu Jingning , Karaplis Andrew C. , Pollak Martin R. , Brown Edward M. , Miao Dengshun , Goltzman David
Published: January 2012

Although the calcium-sensing receptor (CaSR) and parathyroid hormone (PTH) may each exert skeletal effects, it is uncertain how CaSR and PTH interact at the level of bone in primary hyperparathyroidism (PHPT). Therefore, we simulated PHPT with 2 wk of continuous PTH infusion in adult mice with deletion of the PTH gene ( Pth−/− mice) and with deletion of both PTH and CaSR genes ( Pth−/−- Casr −/− mice) and compared skeletal phenotypes. PTH infusion in Pth−/− mice increased cortical bone turnover, augmented cortical porosity, and reduced cortical bone volume, femoral bone mineral density (BMD), and bone mineral content (BMC); these effects were markedly attenuated in PTH-infused Pth−/−- Casr−/− mice. In the absence of CaSR, the PTH-stimulated expression of receptor activator of nuclear factor-κB ligand and tartrate-resistant acid phosphatase and PTH-stimulated osteoclastogenesis was also reduced. In trabecular bone, PTH-induced increases in bone turnover, trabecular bone volume, and trabecular number were lower in Pth−/−- Casr−/− mice than in Pth−/− mice. PTH-stimulated genetic markers of osteoblast activity were also lower. These results are consistent with a role for CaSR in modulating both PTH-induced bone resorption and PTH-induced bone formation in discrete skeletal compartments.
Synthesis, Characterization, and Biological Activity of Some Transition Metal Complexes Derived from Novel Hydrazone Azo Schiff Base Ligand
Authors: Anitha C. , Sumathi S. , Tharmaraj P. , Sheela C. D.
Published: January 2012

A series of metal(II) complexes ML where M = VO(II), Co(II), Ni(II), Cu(II), and Zn(II) have been synthesized from azo Schiff base ligand (N′E)-N′-(5-((4-chlorophenyl)diazenyl)-2-hydroxybenzylidene)-2-hydroxybenzohydrazide and characterized on the basis of elemental analyses, electronic, IR, and 1H NMR spectra, magnetic susceptibility and also by aid of scanning electron microscopy (SEM), X-ray powder diffraction, fluorescence spectral studies, and molar conductivity measurements. Conductivity measurements reveal that the complexes are nonelectrolytes. Spectroscopy and other analytical studies reveal distorted square planar geometry for copper, square-pyramidal geometry for oxovanadium, and tetrahedral geometry for other complexes. Redox behavior of the copper(II) complex has been studied with cyclic voltammetry, and the biological activities of the ligand and metal complexes have been studied against several microorganisms by the well diffusion method. All synthesized compounds can serve as potential photoactive materials as indicated from their characteristic fluorescence properties. The second harmonic generation (SHG) efficiency of the ligand was measured and found to be higher than that of urea and KDP. The SEM image of the copper(II) complex implies that the size of the particles is 50 nm.
Proximity of Residence to Bodies of Water and Risk for West Nile Virus Infection: A Case-Control Study in Houston, Texas
Authors: Nolan Melissa S. , Zangeneh Ana , Khuwaja Salma A. , Martinez Diana , Rossmann Susan N. , Cardenas Victor , Murray Kristy O.
Published: January 2012

West Nile virus (WNV), a mosquito-borne virus, has clinically affected hundreds of residents in the Houston metropolitan area since its introduction in 2002. This study aimed to determine if living within close proximity to a water source increases one’s odds of infection with WNV. We identified 356 eligible WNV-positive cases and 356 controls using a population proportionate to size model with US Census Bureau data. We found that living near slow moving water sources was statistically associated with increased odds for human infection, while living near moderate moving water systems was associated with decreased odds for human infection. Living near bayous lined with vegetation as opposed to concrete also showed increased risk of infection. The habitats of slow moving and vegetation lined water sources appear to favor the mosquito-human transmission cycle. These methods can be used by resource-limited health entities to identify high-risk areas for arboviral disease surveillance and efficient mosquito management initiatives.
Wound Healing and Anti-Inflammatory Effect in Animal Models ofCalendula officinalisL. Growing in Brazil
Authors: Parente Leila Maria Leal , Lino Júnior Ruy de Souza , Tresvenzol Leonice Manrique Faustino , Vinaud Marina Clare , de Paula José Realino , Paulo Neusa Margarida
Published: January 2012

Calendula officinalisis an annual herb from Mediterranean origin which is popularly used in wound healing and as an anti-inflammatory agent. In this study, the ethanolic extract, the dichloromethane, and hexanic fractions of the flowers from plants growing in Brazil were produced. The angiogenic activity of the extract and fractions was evaluated through the chorioallantoic membrane and cutaneous wounds in rat models. The healing activity of the extract was evaluated by the same cutaneous wounds model through macroscopic, morphometric, histopathologic, and immunohistochemical analysis. The antibacterial activity of the extract and fractions was also evaluated. This experimental study revealed thatC. officinalispresented anti-inflammatory and antibacterial activities as well as angiogenic and fibroplastic properties acting in a positive way on the inflammatory and proliferative phases of the healing process.
Quantifying Cell-to-Cell Variations in Lithium Ion Batteries
Authors: Santhanagopalan Shriram , White Ralph E.
Published: January 2012

Lithium ion batteries have conventionally been manufactured in small capacities but large volumes for consumer electronics applications. More recently, the industry has seen a surge in the individual cell capacities, as well as the number of cells used to build modules and packs. Reducing cell-to-cell and lot-to-lot variations has been identified as one of the major means to reduce the rejection rate when building the packs as well as to improve pack durability. The tight quality control measures have been passed on from the pack manufactures to the companies building the individual cells and in turn to the components. This paper identifies a quantitative procedure utilizing impedance spectroscopy, a commonly used tool, to determine the effects of material variability on the cell performance, to compare the relative importance of uncertainties in the component properties, and to suggest a rational procedure to set quality control specifications for the various components of a cell, that will reduce cell-to-cell variability, while preventing undue requirements on uniformity that often result in excessive cost of manufacturing but have a limited impact on the cells' performance.
Effective Larval Foraging in Large, Low-Diet Environments byAnopheles gambiae
Authors: Sutcliffe A. C. , Benedict M. Q.
Published: January 2012

Adult mosquito size is constrained by conditions experienced in the larval stage including the amount and quality of diet. The energy expended collecting diet depends partly on its concentration, the water depth, and the mosquito species. In order to better understand these interactions, individualAnopheles gambiaes.s. Giles were cultured to the adult stage in three types of experiments in which one of the following conditions was fixed and the other two were varied: water volume, diet amount, and diet concentration. In addition to survival, days of development to pupation and wing length were determined. The same outcomes were measured in experiments for which special containers were constructed that allowed the detection of chemical and tactile interactions. Larvae were able to develop to adulthood in volumes as great as 30 mL/larva when diet was added at an average rate of only 7 μg/mL/day. The results demonstrate effective foraging in large low-diet volumes far above what had previously been estimated.
Accelerated Growth Rate Induced by Neonatal High-Protein Milk Formula Is Not Supported by Increased Tissue Protein Synthesis in Low-Birth-Weight Piglets
Authors: Jamin Agnès , Sève Bernard , Thibault Jean-Noël , Floc’h Nathalie
Published: January 2012

Low-birth-weight neonates are routinely fed a high-protein formula to promote catch-up growth and antibiotics are usually associated to prevent infection. Yet the effects of such practices on tissue protein metabolism are unknown. Baby pigs were fed from age 2 to 7 or 28 d with high protein formula with or without amoxicillin supplementation, in parallel with normal protein formula, to determine tissue protein metabolism modifications. Feeding high protein formula increased growth rate between 2 and 28 days of age when antibiotic was administered early in the first week of life. This could be explained by the occurrence of diarrhea when piglets were fed the high protein formula alone. Higher growth rate was associated with higher feed conversion and reduced protein synthesis rate in the small intestine, muscle and carcass, whereas proteolytic enzyme activities measured in these tissues were unchanged. In conclusion, accelerated growth rate caused by high protein formula and antibiotics was not supported by increased protein synthesis in muscle and carcass.
New Traveling Wave Solutions of the Higher Dimensional Nonlinear Partial Differential Equation by the Exp‐Function Method
Authors: Naher Hasibun , Abdullah Farah Aini , Akbar M. Ali
Published: January 2012

We construct new analytical solutions of the (3 + 1)‐dimensional modified KdV‐Zakharov‐Kuznetsev equation by the Exp‐function method. Plentiful exact traveling wave solutions with arbitrary parameters are effectively obtained by the method. The obtained results show that the Exp‐function method is effective and straightforward mathematical tool for searching analytical solutions with arbitrary parameters of higher‐dimensional nonlinear partial differential equation.
Novel Compact Multiband MIMO Antenna for Mobile Terminal
Authors: Yang Cheng , Yao Yuan , Yu Junsheng , Chen Xiaodong
Published: January 2012

A novel compact MIMO antenna for personal digital assistant (PDA) and pad computer is proposed. The proposed antenna is composed by two multipatch monopole antennas which are placed 90° apart for orthogonal radiation. To strengthen the isolation, a T-shaped ground branch with proper dimension is used to generate an additional coupling path to lower the mutual coupling (below −15 dB), especially at GSM850/900 band. The proposed MIMO antenna is fabricated and tested, both the simulated and the measured results are presented, and some parametric studies are also demonstrated. In addition, there are some advantages about the proposed antenna such as simple structure, easy fabrication, and low cost.
One-Step Synthesized Pt-on-NiCo Nanostructures for Oxygen Reduction with High Activity and Long-Term Stability
Authors: Qu Qiang , Wen Ming , Cheng Mingzhu , Zhu Anwei , Kong Biao , Tian Yang
Published: January 2012

A novel particle-on-alloy nanomaterial has been designed and successfully synthesized for oxygen reduction (ORR) with high activity and long-term stability, in which well-isolated Pt nanoparticles are supported by amorphous NiCo nanoalloys. The Pt-on-NiCo nanostructures are prepared through the artificial active collodion membrane by one-step method, and experimental data reveals that Pt is isolated and spreads onto the amorphous NiCo nanosupport, and not only Pt but also Ni and Co are metallic in the Pt-on-NiCo nanostructures. The optimized Pt53-on-NiCo nanostructures show higher activities in both the onset potential and kinetic current density toward the ORR relative to the commercial Pt reference catalysts because the Pt-on-NiCo catalyst could lower theOHad, which is considered to inhibit the ORR toward water. Meanwhile, Pt-on-NiCo nanostructures exhibit relatively long-term stability with only ~8% loss in electrochemical surface area (ECSA) for Pt.
Constitutive AP-1 Activity and EBV Infection Induce PD-L1 in Hodgkin Lymphomas and Posttransplant Lymphoproliferative Disorders: Implications for Targeted Therapy
Authors: Green Michael R. , Rodig Scott , Juszczynski Przemyslaw , Ouyang Jing , Sinha Papiya , O'Donnell Evan , Neuberg Donna , Shipp Margaret A.
Published: January 2012

Purpose: Programmed cell death ligand 1 (PD-L1) is a molecule expressed on antigen-presenting cells that engages the PD-1 receptor on T cells and inhibits T-cell receptor signaling. The PD-1 axis can be exploited by tumor cells to dampen host antitumor immune responses and foster tumor cell survival. PD-1 blockade has shown promise in multiple malignancies but should be directed toward patients in whom it will be most effective. In recent studies, we found that the chromosome 9p24.1 amplification increased the gene dosage of PD-L1 and its induction by JAK2 in a subset of patients with classical Hodgkin lymphoma (cHL). However, cHLs with normal 9p24.1 copy numbers also expressed detectable PD-L1, prompting analyses of additional PD-L1 regulatory mechanisms.

Experimental Design: Herein, we utilized immunohistochemical, genomic, and functional analyses to define alternative mechanisms of PD-L1 activation in cHL and additional EBV+ lymphoproliferative disorders.

Results: We identified an AP-1–responsive enhancer in the PD-L1 gene. In cHL Reed–Sternberg cells, which exhibit constitutive AP-1 activation, the PD-L1 enhancer binds AP-1 components and increases PD-L1 promoter activity. In addition, we defined Epstein–Barr virus (EBV) infection as an alternative mechanism for PD-L1 induction in cHLs with diploid 9p24.1. PD-L1 was also expressed by EBV-transformed lymphoblastoid cell lines as a result of latent membrane protein 1–mediated, JAK/STAT-dependent promoter and AP-1–associated enhancer activity. In addition, more than 70% of EBV+ posttransplant lymphoproliferative disorders expressed detectable PD-L1.

Conclusions: AP-1 signaling and EBV infection represent alternative mechanisms of PD-L1 induction and extend the spectrum of tumors in which to consider PD-1 blockade. Clin Cancer Res; 18(6); 1611–8. ©2012 AACR.
Combined MEK and VEGFR Inhibition in Orthotopic Human Lung Cancer Models Results in Enhanced Inhibition of Tumor Angiogenesis, Growth, and Metastasis
Authors: Takahashi Osamu , Komaki Ritsuko , Smith Paul D. , Jürgensmeier Juliane M. , Ryan Anderson , Bekele B. Nebiyou , Wistuba Ignacio I. , Jacoby Jörg J. , Korshunova Maria V. , Biernacka Anna , Erez Baruch , Hosho Keiko , Herbst Roy S. , O'Reilly Michael S.
Published: January 2012

Purpose: Ras/Raf/mitogen-activated protein–extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK signaling is critical for tumor cell proliferation and survival. Selumetinib is a potent, selective, and orally available MEK1/2 inhibitor. In this study, we evaluated the therapeutic efficacy of selumetinib alone or with cediranib, an orally available potent inhibitor of all three VEGF receptor (VEGFR) tyrosine kinases, in murine orthotopic non–small cell lung carcinoma (NSCLC) models.

Experimental Design: NCI-H441 or NCI-H460 KRAS-mutant human NSCLC cells were injected into the lungs of mice. Mice were randomly assigned to treatment with selumetinib, cediranib, paclitaxel, selumetinib plus cediranib, or control. When controls became moribund, all animals were sacrificed and assessed for lung tumor burden and locoregional metastasis. Lung tumors and adjacent normal tissues were subjected to immunohistochemical analyses.

Results: Selumetinib inhibited lung tumor growth and, particularly at higher dose, reduced locoregional metastasis, as did cediranib. Combining selumetinib and cediranib markedly enhanced their antitumor effects, with near complete suppression of metastasis. Immunohistochemistry of tumor tissues revealed that selumetinib alone or with cediranib reduced ERK phosphorylation, angiogenesis, and tumor cell proliferation and increased apoptosis. The antiangiogenic and apoptotic effects were substantially enhanced when the agents were combined. Selumetinib also inhibited lung tumor VEGF production and VEGFR signaling.

Conclusions: In this study, we evaluated therapy directed against MEK combined with antiangiogenic therapy in distinct orthotopic NSCLC models. MEK inhibition resulted in potent antiangiogenic effects with decreased VEGF expression and signaling. Combining selumetinib with cediranib enhanced their antitumor and antiangiogenic effects. We conclude that combining selumetinib and cediranib represents a promising strategy for the treatment of NSCLC. Clin Cancer Res; 18(6); 1641–54. ©2012 AACR.
A20 Ubiquitin Ligase–Mediated Polyubiquitination of RIP1 Inhibits Caspase-8 Cleavage and TRAIL-Induced Apoptosis in Glioblastoma
Authors: Bellail Anita C. , Olson Jeffrey J. , Yang Xiaolu , Chen Zhijian J. , Hao Chunhai
Published: January 2012

The TNF-related apoptosis-inducing ligand (TRAIL) apoptotic pathway has emerged as a therapeutic target for the treatment of cancer. However, clinical trials have proven that the vast majority of human cancers are resistant to TRAIL apoptotic pathway-targeted therapies. We show that A20-mediated ubiquitination inhibits caspase-8 cleavage and TRAIL-induced apoptosis in glioblastoma through 2 signaling complexes. A20 is highly expressed in glioblastomas and, together with the death receptor 5 and receptor-interacting protein 1, forms a plasma membrane-bound preligand assembly complex under physiologic conditions. Treatment with TRAIL leads to the recruitment of caspase-8 to the plasma membrane-bound preligand assembly complex for the assembly of a death-inducing signaling complex. In the death-inducing signaling complex, the C-terminal zinc finger (Znf) domain of the A20 ubiquitin ligase mediates receptor-interacting protein 1 polyubiquitination through lysine-63-linked polyubiquitin chains, which bind to the caspase-8 protease domain and inhibit caspase-8 dimerization, cleavage, and the initiation of TRAIL-induced apoptosis in glioblastoma-derived cell lines and tumor-initiating cells.

Significance: These results identify A20 E3 ligase as a therapeutic target whose inhibition can overcome TNF-related apoptosis-inducing ligand resistance in glioblastoma and thus have an impact on ongoing clinical trials of TNF-related apoptosis-inducing ligand-targeted combination cancer therapies. Cancer Discovery; 2(2); 140–55. © 2012 AACR.

Read the Commentary on this article by Verbrugge and Johnstone, p. 112.

This article is highlighted in the In This Issue feature, p. 95.
Analysis of RCAS1 Immunoreactivity within Hydatidiform Mole Cells and Decidual Cells according to the Applied Therapeutic Strategy: Surgery or Surgery Followed by Chemotherapy
Authors: Wicherek Lukasz , Basta Pawel , Wertel Iwona , Kojs Zbigniew , Malkowski Bogdan , Grabiec Marek , Pietrus Milosz , Krystyna Galazka
Published: January 2012

Introduction: Trophoblast cells cooperate with both maternal immune cells and decidual cells to help develop the suppressive microenvironment of the endometrium. The maternal immune response against hydatidiform mole depends on this suppressive endometrial profile. Since RCAS1 is one of the molecular factors participating in the development of the suppressive profile of the endometrium we decided to examine the immunoreactivity of the RCAS1 within both the trophoblast and decidual cells during the development of hydatidiform mole. Methods: We analyzed the immunoreactivity of RCAS1 on both trophoblast and decidual cells derived from patients who underwent curettage because of hydatidiform mole. These patients were then divided into two subgroups according to whether or not they required chemotherapy after the surgical procedure. Result: We observed significantly lower immunoreactivity levels of both RCAS1 within the complete molar lesions of the patients on whom surgery alone was performed when compared to the levels found in those for whom surgery was followed by chemotherapy. Conclusion: RCAS1 staining may provide information regarding the intensity of the immunosuppressive microenvironment of both the molar lesion and the endometrium. This information can prove significant in determining the clinical course of hydatidiform mole.