bluuebunny/crossref_metadata_2025 huggingface dataset:
Gravitational wave science in the high school classroom
Authors: Farr Benjamin , Schelbert GionMatthias , Trouille Laura
Published: September 2012

This article describes a set of curriculum modifications designed to integrate gravitational wave science into a high school physics or astronomy curriculum. Gravitational wave scientists are on the verge of being able to detect extreme cosmic events, like the merger of two black holes, happening hundreds of millions of light years away. Their work has the potential to propel astronomy into a new era by providing an entirely new means of observing astronomical phenomena. Gravitational wave science encompasses astrophysics, physics, engineering, and quantum optics. As a result, this curriculum exposes students to the interdisciplinary nature of science. It also provides an authentic context for students to learn about astrophysical sources, data analysis techniques, cutting-edge detector technology, and error analysis.
Modulating Mitochondrial Intracellular Location as a Redox Signal
Authors: Murphy Michael P.
Published: September 2012

Hypoxia induces the redistribution of mitochondria to promote transcriptional responses to low oxygen.
It’s the Pits
Authors: Hines Pamela J.
Published: September 2012

A Rho guanosine triphosphatase–based regulatory mechanism reveals how plants remodel membranes and cell walls to produce various cell shapes.
Timing the Immune Response
Authors: Gough Nancy R.
Published: September 2012

The circadian regulator CLOCK enhances the transcriptional activity of the immune regulator NF-κB.
Influence of the Protein Kinase C Activator Phorbol Myristate Acetate on the Intracellular Activity of Antibiotics against Hemin- and Menadione-Auxotrophic Small-Colony Variant Mutants of Staphylococcus aureus and Their Wild-Type Parental Strain in Human THP-1 Cells
Authors: Garcia Laetitia G. , Lemaire Sandrine , Kahl Barbara C. , Becker Karsten , Proctor Richard A. , Tulkens Paul M. , Van Bambeke Françoise
Published: September 2012

In a previous study (L. G. Garcia et al., Antimicrob. Agents Chemother. 56:3700–3711, 2012), we evaluated the intracellular fate of
menD
and
hemB
mutants (corresponding to menadione- and hemin-dependent small-colony variants, respectively) of the parental COL methicillin-resistant
Staphylococcus aureus
strain and the pharmacodynamic profile of the intracellular activity of a series of antibiotics in human THP-1 monocytes. We have now examined the phagocytosis and intracellular persistence of the same strains in THP-1 cells activated by phorbol 12-myristate 13-acetate (PMA) and measured the intracellular activity of gentamicin, moxifloxacin, and oritavancin in these cells. Postphagocytosis intracellular counts and intracellular survival were lower in PMA-activated cells, probably due to their higher killing capacities. Gentamicin and moxifloxacin showed a 5- to 7-fold higher potency (lower static concentrations) against the parental strain, its
hemB
mutant, and the genetically complemented strain in PMA-activated cells and against the
menD
strain in both activated and nonactivated cells. This effect was inhibited when cells were incubated with
N
-acetylcysteine (a scavenger of oxidant species). In parallel, we observed that the MICs of these drugs were markedly reduced if bacteria had been preexposed to H
2
O
2
. In contrast, the intracellular potency of oritavancin was not different in activated and nonactivated cells and was not decreased by the addition of
N
-acetylcysteine, regardless of the phenotype of the strains. The oritavancin MIC was also unaffected by preincubation of the bacteria with H
2
O
2
. Thus, activation of THP-1 cells by PMA may increase the intracellular potency of certain antibiotics (probably due to synergy with reactive oxygen species), but this effect cannot be generalized to all antibiotics.
Efficacy of Ceftaroline Fosamil in a Staphylococcal Murine Pneumonia Model
Authors: Bhalodi Amira A. , Crandon Jared L. , Biek Donald , Nicolau David P.
Published: September 2012

Ceftaroline fosamil is a cephalosporin with activity against Gram-positive pathogens, including methicillin-resistant
Staphylococcus aureus
(MRSA). The objective of this study was to characterize the dose-response relationship of ceftaroline fosamil against
S. aureus
in an immunocompromised murine pneumonia model, as well as to evaluate the efficacy of the humanized regimen of 600 mg intravenously (i.v.) every 12 h. Seventeen
S. aureus
(2 methicillin-susceptible
Staphylococcus aureus
[MSSA], 15 MRSA) isolates with ceftaroline MICs of 0.5 to 4 μg/ml were utilized. The pharmacokinetics of ceftaroline in serum and epithelial lining fluid (ELF) were evaluated to determine bronchopulmonary exposure profiles in infected and uninfected animals, using single and human-simulated doses. Serum
f
T>MIC (the percentage of time that free drug concentrations remain above the MIC) of 17% to 43% was required to produce a 1-log
10
kill in the dose-ranging studies. These targets were readily achieved with the humanized exposure profile, where decreases of 0.64 to 1.95 log
10
CFU were observed against 13 MRSA and both MSSA isolates tested. When taken as a composite, the
f
T>MICs required for stasis and a 1-log
10
kill were 16% and 41%, respectively. ELF concentrations were similar to serum concentrations across the dosing interval in infected and uninfected animals. The serum
f
T>MIC targets required in this lung infection model were similar to those observed with ceftaroline against
S. aureus
in a murine thigh infection model. Exposures simulating the human dose of 600 mg i.v. every 12 h achieved pharmacodynamic targets against MRSA and MSSA considered susceptible by current U.S. FDA breakpoints.
Susceptibility to Progressive Cryptococcus neoformans Pulmonary Infection Is Regulated by Loci on Mouse Chromosomes 1 and 9
Authors: Carroll Scott F. , Lafferty Erin I. , Flaczyk Adam , Fujiwara T. Mary , Homer Robert , Morgan Kenneth , Loredo-Osti J C. , Qureshi Salman T.
Published: September 2012

Genetic factors that regulate the pathogenesis of pneumonia caused by the fungusCryptococcus neoformansare poorly understood. Through a phenotypic strain survey we observed that inbred C3H/HeN mice develop a significantly greater lung fungal burden than mice of the resistant CBA/J strain 4 weeks following intratracheal infection withC. neoformansATCC 24067. The aim of the present study was to characterize the inflammatory response of C3H/HeN mice followingC. neoformanspulmonary infection and to identify genetic loci that regulate host defense. Following cryptococcal infection, C3H/HeN mice demonstrated a Th2 immune response with heightened airway and tissue eosinophilia, goblet cell metaplasia, and significantly higher lung interleukin-5 (IL-5) and IL-13 protein expression relative to CBA/J mice. Conversely, CBA/J mice exhibited greater airway and tissue neutrophilia that was associated with significantly higher pulmonary expression of gamma interferon, CXCL10, and IL-17 proteins than C3H/HeN mice. Using the fungal burden at 4 weeks postinfection as a phenotype, genome-wide quantitative trait locus (QTL) analysis among 435 segregating (C3H/HeN × CBA/J)F2 (C3HCBAF2) hybrids identified two significant QTLs on chromosomes 1 (Cnes4) and 9 (Cnes5) that control susceptibility to cryptococcal pneumonia in an additive manner. Susceptible C3H/HeN mice carry a resistance allele atCnes4and a susceptibility allele atCnes5. These studies reveal additional genetic complexity of the host response toC. neoformansthat is associated with divergent patterns of pulmonary inflammation.
Cyclic Di-GMP Stimulates Biofilm Formation and Inhibits Virulence of Francisella novicida
Authors: Zogaj Xhavit , Wyatt Geoff C. , Klose Karl E.
Published: September 2012

Francisella tularensisis a Gram-negative bacterium that is highly virulent in humans, causing the disease tularemia.F. novicidais closely related toF. tularensisand exhibits high virulence in mice, but it is avirulent in healthy humans. AnF. novicida-specific gene cluster (FTN0451 to FTN0456) encodes two proteins with diguanylate cyclase (DGC) and phosphodiesterase (PDE) domains that modulate the synthesis and degradation of cyclic di-GMP (cdGMP). No DGC- or PDE-encoding protein genes are present in theF. tularensisgenome.F. novicidastrains lacking either the two DGC/PDE genes (cdgAandcdgB) or the entire gene cluster (strain KKF457) are defective for biofilm formation. In addition, expression of CdgB or a heterologous DGC in strain KKF457 stimulatedF. novicidabiofilms, even in a strain lacking the biofilm regulator QseB. Genetic evidence suggests that CdgA is predominantly a PDE, while CdgB is predominantly a DGC. TheF. novicida qseBstrain showed reducedcdgAandcdgBtranscript levels, demonstrating anF. novicidabiofilm signaling cascade that controls cdGMP levels. Interestingly, KKF457 with elevated cdGMP levels exhibited a decrease in intramacrophage replication and virulence in mice, as well as increased growth yields and biofilm formationin vitro. Microarray analyses revealed that cdGMP stimulated the transcription of a chitinase (ChiB) known to contribute to biofilm formation. Our results indicate that elevated cdGMP inF. novicidastimulates biofilm formation and inhibits virulence. We suggest that differences in human virulence betweenF. novicidaandF. tularensismay be due in part to the absence of cdGMP signaling inF. tularensis.
Involvement of Signal Regulatory Protein α, a Negative Regulator of Toll-Like Receptor Signaling, in Impairing the MyD88-Independent Pathway and Intracellular Killing of Burkholderia pseudomallei-Infected Mouse Macrophages
Authors: Baral Pankaj , Utaisincharoen Pongsak
Published: September 2012

The facultative intracellular Gram-negative bacterium
Burkholderia pseudomallei
is the causative agent of melioidosis and is known for its ability to evade the Toll-like receptor (TLR)-mediated innate immune response. Previously it has been demonstrated that this bacterium was able to suppress the MyD88-independent pathway and can survive macrophage intracellular killing. However, the underlying mechanisms responsible for the suppression of this pathway are not fully understood. In the present study, we showed that both living and heat-killed
B. pseudomallei
bacteria restrict the TLR signaling response, particularly macrophage inducible nitric oxide synthase (iNOS) expression, by preventing downregulation of constitutively expressed signal regulatory protein α (SIRPα) molecule, a known negative regulator of TLR signaling. In contrast, a lipopolysaccharide (LPS) mutant of
B. pseudomallei
, a less virulent strain, was able to downregulate SIRPα expression in mouse macrophages. However, depletion of constitutively expressed SIRPα was able to induce the gene expression downstream of TLR signaling pathways (particularly the MyD88-independent pathway), such as that of the iNOS gene, leading to enhanced macrophage intracellular killing of
B. pseudomallei
. Induction of gene expression was consistent with the enhanced degradation pattern of IκBα with SIRPα depletion. Additionally, the downregulation of SIRPα expression with upregulation of iNOS was observed when the macrophages were pretreated with gamma interferon (IFN-γ) prior to the infection, suggesting that the enhanced intracellular killing of bacteria by IFN-γ is associated with the decreased SIRPα expression. Altogether our findings demonstrate that
B. pseudomallei
evades macrophage intracellular killing by preventing the downregulation of SIRPα that results in the inhibition of gene expression downstream of the MyD88-independent pathway.
Nocardia farcinica Activates Human Dendritic Cells and Induces Secretion of Interleukin-23 (IL-23) Rather than IL-12p70
Authors: Eisenblätter Martin , Buchal Ariane , Gayum Hermine , Jasny Edith , Renner Viveros Pablo , Ulrichs Timo , Schneider Thomas , Schumann Ralf R. , Zweigner Janine , Ignatius Ralf
Published: September 2012

Studying the interaction of dendritic cells (DCs) with bacteria controlled by T-cell-mediated immune responses may reveal novel adjuvants for the induction of cellular immunity. Murine studies and the observation that nocardias infect predominantly immunosuppressed patients have suggested that these bacteria may possess an adjuvant potential. Moreover, adjuvants on the basis of the nocardial cell wall have been applied in clinical studies. Since the handling of adjuvants by DCs may determine the type of immune responses induced by a vaccine, the present study aimed at investigating the interaction of immature human monocyte-derived DCs with live or inactivatedNocardia farcinicain vitroand determining the cellular phenotypic changes as well as alterations in characteristic functions, such as phagocytosis, induction of T-cell proliferation, and cytokine secretion. Human DCs ingestedN. farcinicaand eradicated the bacterium intracellularly. DCs exposed to inactivatedN. farcinicawere activated, i.e., they developed a mature phenotype, downregulated their phagocytic capacity, and stimulated allogeneic T cells in mixed leukocyte reactions. Soluble factors were not involved in this process. To elucidate the potential adjuvant effect ofN. farcinicaon the induction of T-cell-mediated immune responses, we characterized the cytokines produced by nocardia-exposed DCs and detected substantial amounts of tumor necrosis factor alpha (TNF-α) and interleukin-12 p40 (IL-12p40). However, nocardia-treated DCs secreted only small amounts of IL-12p70, which were significantly smaller than the amounts of IL-23. Thus,N. farcinicaactivates DCs, but adjuvants based on this bacterium may have only a limited capacity to induce Th1 immune responses.
LINEAR SERIES ON CURVES: STABILITY AND CLIFFORD INDEX
Authors: MISTRETTA ERNESTO C. , STOPPINO LIDIA
Published: September 2012

We study concepts of stability associated to a smooth complex curve together with a linear series on it. In particular we investigate the relation between stability of the associated dual span bundle and linear stability. Our results imply that stability of the dual span holds under a hypothesis related to the Clifford index of the curve. Furthermore, in some of the cases, we prove that a stronger stability holds: cohomological stability. Finally, using our results we obtain stable vector bundles of slope 3, and prove that they admit theta-divisors.
SINE–GORDON THEORY IN THE REPULSIVE REGIME, THERMODYNAMIC BETHE ANSATZ AND MINIMAL MODELS
Authors: ITOYAMA H.
Published: September 2012

Neutral excitations present in the repulsive regime (1/2 < β2/8π < 1) of the sine–Gordon/massive–Thirring model and its study of the massless limit by the thermodynamic Bethe ansatz is revisited. At β2/8π = 1-1/(p+1) the solitons become infinitely heavy, forcing truncation to the neutral excitations alone. The central charge in this limit is calculated to be c = 1-6/p(p+1); the mass and S-matrices of the truncated theories are identified as those of the minimal conformal theory Mp perturbed by the ϕ(1, 3) operator.
Investigation of Energy-Dispersive X-ray Computed Tomography System with CdTe Scan Detector and Comparing-Differentiator and Its Application to Gadolinium K-Edge Imaging
Authors: Chiba Hiraku , Sato Yuichi , Sato Eiichi , Maeda Tomoko , Matsushita Ryo , Yanbe Yutaka , Hagiwara Osahiko , Matsukiyo Hiroshi , Osawa Akihiro , Enomoto Toshiyuki , Watanabe Manabu , Kusachi Shinya , Sato Shigehiro , Ogawa Akira , Onagawa Jun
Published: September 2012

An energy-dispersive (ED) X-ray computed tomography (CT) system is useful for carrying out monochromatic imaging by selecting optimal energy photons. CT is performed by repeated linear scans and rotations of an object. X-ray photons from the object are detected by the cadmium telluride (CdTe) detector, and event pulses of X-ray photons are produced using charge-sensitive and shaping amplifiers. The lower photon energy is determined by a comparator, and the maximum photon energy of 70 keV corresponds to the tube voltage. Logical pulses from the comparator are counted by a counter card through a differentiator to reduce pulse width and rise time. In the ED-CT system, tube voltage and current were 70 kV and 0.30 mA, respectively, and X-ray intensity was 18.2 µGy/s at 1.0 m from the source at a tube voltage of 70 kV. Demonstration of gadolinium K-edge CT for cancer diagnosis was carried out by selecting photons with energies ranging from 50.4 to 70 keV, and photon-count energy subtraction imaging from 30 to 50.3 keV was also performed.
Correlation between Switching Field and Microstructure of Individual Co/Pt Dots
Authors: Kikuchi Nobuaki , Murayama Yusuke , Murakami Yasukazu , Okamoto Satoshi , Shindo Daisuke , Kitakami Osamu
Published: September 2012

The correlation between the microstructure and the magnetization switching field of individual Co/Pt multilayer nanodots with Pt or Ta/Pt underlayers has been investigated by transmission electron microscopy and magnetic force microscopy. The insertion of a 2-nm-thick Ta underlayer promoted the Co/Pt [111] crystal axis orientation and improved the mean switching field and the switching field distribution of nanodot arrays with a diameter of 70 nm from 1.4 to 6.9 kOe and from 22 to 8%, respectively. Electron microscopy of individual dots has revealed that all the nanodots without the Ta layer contain (200)-oriented grains, which possibly work as nucleation sites owing to a small perpendicular magnetic anisotropy. However, no structural difference is found among the dots having the same underlayers, suggesting the existence of other factors affecting the switching field distribution.
Dependence of Dissolution Point on Pattern Size of Chemically Amplified Extreme Ultraviolet Resist
Authors: Kozawa Takahiro , Santillan Julius Joseph , Itani Toshiro
Published: September 2012

The dependence of dissolution point on pattern size was investigated using a chemically amplified extreme ultraviolet resist to clarify the effect of pattern size on the solubility of resist polymers in a developer. The dissolution point decreased with the decrease in the pitch of line-and-space patterns. This result suggests that the amount of chemical reactions required to dissolve polymer molecules increased with the decrease in pattern size.
A new workflow for carbonate reservoir modelling based on MPS: shoal bodies in outcrop analogues (Triassic, SW Germany)
Authors: Jung Andre , Aigner Thomas , Palermo Denis , Nardon Sergio , Pontiggia Marco
Published: September 2012

This study presents a workflow for 3D modelling of carbonate reservoirs using multiple-point statistics (MPS) in the framework of a pre-existing model. It consists of the following steps: (1) applying a hierarchical classification scheme for carbonate geobodies; (2) based on this classification, retrieval of relevant data from Carbdb, a novel software to manage a database of analogue studies; (3) construction of training images based on the retrieved data from Carbdb; and (4) using the training images when building a 3D reservoir model with MPS. MPS makes use of training images to capture depositional patterns, which will then be reproduced during the stochastic simulations. Carbdb provides a library of quantitative data such as dimensions, geometries and the distribution pattern of geobody analogues necessary for building training images. The MPS workflow was applied to carbonate shoal bodies from a reservoir analogue, the Muschelkalk in SW Germany. Present-day shoal bodies from the Arabian Gulf were retrieved from Carbdb as possible modern analogues to generate training images. The realizations of this MPS approach are compared with a previously established 3D geocellular model that was built deterministically by interactive facies modelling. The MPS simulations produced geologically more realistic facies distributions with higher facies heterogeneity, similar to the depositional patterns observed in modern analogues.
Biosorption of Mercury (II) from Aqueous Solutions onto Fungal Biomass
Authors: Martínez-Juárez Víctor M. , Cárdenas-González Juan F. , Torre-Bouscoulet María Eugenia , Acosta-Rodríguez Ismael
Published: September 2012

The biosorption of mercury (II) on 14 fungal biomasses,Aspergillus flavusI–V,Aspergillus fumigatusI-II,Helminthosporiumsp.,Cladosporiumsp.,Mucor rouxiimutant,M. rouxiiIM-80,Mucorsp 1 and 2, andCandida albicans, was studied in this work. It was found that the biomasses of the fungusM. rouxiiIM-80,M. rouxiimutant,Mucorsp1, andMucorsp 2 were very efficient removing the metal in solution, using dithizone, reaching the next percentage of removals: 95.3%, 88.7%, 80.4%, and 78.3%, respectively. The highest adsorption was obtained at pH 5.5, at 30°C after 24 hours of incubation, with 1 g/100 mL of fungal biomass.
Salvage Therapy for Refractory Aids-Related Primary Central Nervous System Lymphoma
Authors: Ferro Hugo , Parino Eduardo
Published: September 2012

A 27-year-old male patient presented with speech disorders and multiple brain masses on MRI evaluation. He tested positive for HIV. A sterotactic biopsy diagnosed primary central nervous system lymphoma (diffuse large B-cell lymphoma). After two cycles of high-dose metotrexate (HD-MTX-)-based chemotherapy, the tumor progressed. He underwent whole brain radiotherapy achieving complete response. Six cycles of consolidating immunochemotherapy with rituximab-temozolomide were administered after radiation. Forty-three months after remission, he has not recurred and his neurological status is optimal. Younger HIV patients with refractory PCNSL and preserved immune function can face salvage therapy successfully achieving long term remissions with no remarkable neurotoxicity.
The Molecular Basis of Wound Healing Processes Induced by Lithospermi Radix: A Proteomics and Biochemical Analysis
Authors: Hsiao Chia-Yen , Tsai Tung-Hu , Chak Kin-Fu
Published: September 2012

Lithospermi Radix (LR) is an effective traditional Chinese herb in various types of wound healing; however, its mechanism of action remains unknown. A biochemical and proteomic platform was generated to explore the biological phenomena associated with LR and its active component shikonin. We found that both LR ethanol extracts and shikonin are able to promote cell proliferation by up to 25%. The results of proteomic analysis revealed that twenty-two differentially expressed proteins could be identified when fibroblast cells were treated with LR or shikonin. The functions of those proteins are associated with antioxidant activity, antiapoptosis activity, the regulation of cell mobility, the secretion of collagen, the removal of abnormal proteins, and the promotion of cell proliferation, indicating that the efficacy of LR in wound healing may be derived from a synergistic effect on a number of factors induced by the herbal medicine. Furthermore, an animal model confirmed that LR is able to accelerate wound healing on the flank back of the SD rats. Together these findings help to pinpoint the molecular basis of wound healing process induced by LR.
Visual Agreement Analyses of Traditional Chinese Medicine: A Multiple-Dimensional Scaling Approach
Authors: Lo Lun-Chien , Chiang John Y. , Cheng Tsung-Lin , Shieh Pei-Shuan
Published: September 2012

The study of TCM agreement in terms of a powerful statistical tool becomes critical in providing objective evaluations. Several previous studies have conducted on the issue of consistency of TCM, and the results have indicated that agreements are low. Traditional agreement measures only provide a single value which is not sufficient to justify if the agreement among several raters is strong or not. In light of this observation, a novel visual agreement analysis for TCM via multiple dimensional scaling (MDS) is proposed in this study. If there are clusters present in the raters in a latent manner, MDS can prove itself as an effective distinguisher. In this study, a group of doctors, consisting of 11 experienced TCM practitioners having clinical experience ranging from 3 to 15 years with a mean of 5.5 years from the Chinese Medicine Department at Changhua Christian Hospital (CCH) in Taiwan were asked to diagnose a total of fifteen tongue images, the Eight Principles derived from the TCM theorem. The results of statistical analysis show that, if there are clusters present in the raters in a latent manner, MDS can prove itself as an effective distinguisher.
PPARs Signaling and Cancer in the Gastrointestinal System
Authors: Pazienza Valerio , Vinciguerra Manlio , Mazzoccoli Gianluigi
Published: September 2012

Nowadays, the study of the peroxisome proliferators activated receptors (PPARs) as potential targets for cancer prevention and therapy has gained a strong interest. From a biological point of view, the overall responsibility of PPARs in cancer development and progression is still controversial since several studies report both antiproliferative and tumor-promoting actions for these signaling molecules in human cancer cells and animal models. In this paper, we discuss PPARs functions in the context of different types of gastrointestinal cancer.
Inhibition of HIV Replication by Cyclic and Hairpin PNAs Targeting the HIV-1 TAR RNA Loop
Authors: Upert Gregory , Di Giorgio Audrey , Upadhyay Alok , Manvar Dinesh , Pandey Nootan , Pandey Virendra N. , Patino Nadia
Published: September 2012

Human immunodeficiency virus-1 (HIV-1) replication and gene expression entails specific interaction of the viral protein Tat with its transactivation responsive element (TAR), to form a highly stable stem-bulge-loop structure. Previously, we described triphenylphosphonium (TPP) cation-based vectors that efficiently deliver nucleotide analogs (PNAs) into the cytoplasm of cells. In particular, we showed that the TPP conjugate of a linear 16-mer PNA targeting the apical stem-loop region of TAR impedes Tat-mediated transactivation of the HIV-1 LTRin vitroand also in cell culture systems. In this communication, we conjugated TPP to cyclic and hairpin PNAs targeting the loop region of HIV-1 TAR and evaluated their antiviral efficacy in a cell culture system. We found that TPP-cyclic PNAs containing only 8 residues, showed higher antiviral potency compared to hairpin PNAs of 12 or 16 residues. We further noted that the TPP-conjugates of the 8-mer cyclic PNA as well as the 16-mer linear PNA displayed similar antiviral efficacy. However, cyclic PNAs were shown to be highly specific to their target sequences. This communication emphasizes on the importance of small constrained cyclic PNAs over both linear and hairpin structures for targeting biologically relevant RNA hairpins.
Goal-Directed Mechanical Ventilation: Are We Aiming at the Right Goals? A Proposal for an Alternative Approach Aiming at Optimal Lung Compliance, Guided by Esophageal Pressure in Acute Respiratory Failure
Authors: Soroksky Arie , Esquinas Antonio
Published: September 2012

Patients with acute respiratory failure and decreased respiratory system compliance due to ARDS frequently present a formidable challenge. These patients are often subjected to high inspiratory pressure, and in severe cases in order to improve oxygenation and preserve life, we may need to resort to unconventional measures. The currently accepted ARDSNet guidelines are characterized by a generalized approach in which an algorithm for PEEP application and limited plateau pressure are applied to all mechanically ventilated patients. These guidelines do not make any distinction between patients, who may have different chest wall mechanics with diverse pathologies and different mechanical properties of their respiratory system. The ability of assessing pleural pressure by measuring esophageal pressure allows us to partition the respiratory system into its main components of lungs and chest wall. Thus, identifying the dominant factor affecting respiratory system may better direct and optimize mechanical ventilation. Instead of limiting inspiratory pressure by plateau pressure, PEEP and inspiratory pressure adjustment would be individualized specifically for each patient's lung compliance as indicated by transpulmonary pressure. The main goal of this approach is to specifically target transpulmonary pressure instead of plateau pressure, and therefore achieve the best lung compliance with the least transpulmonary pressure possible.
Exploring Risk Factors for Follicular Lymphoma
Authors: Ambinder Alexander J. , Shenoy Pareen J. , Malik Neha , Maggioncalda Alison , Nastoupil Loretta J. , Flowers Christopher R.
Published: September 2012

Follicular lymphoma (FL) is an indolent malignancy of germinal center B cells with varied incidence across racial groups and geographic regions. Improvements in the classification of non-Hodgkin lymphoma subtypes provide an opportunity to explore associations between environmental exposures and FL incidence. Our paper found that aspects of Western lifestyle including sedentary lifestyle, obesity, and diets high in meat and milk are associated with an increased risk of FL. Diets rich in fruits and vegetables, polyunsaturated fatty acids, vitamin D, and certain antioxidants are inversely associated with FL risk. A medical history of Sjogren's syndrome, influenza vaccination, and heart disease may be associated with FL incidence. Associations between FL and exposure to pesticides, industrial solvents, hair dyes, and alcohol/tobacco were inconsistent. Genetic risk factors include variants at the 6p21.32 region of the MHC II locus, polymorphisms of the DNA repair geneXRCC3, and UV exposure in individuals with certain polymorphisms of the vitamin D receptor. Increasing our understanding of risk factors for FL must involve integrating epidemiological studies of genetics and exposures to allow for the examination of risk factors and interactions between genes and environment.
New Fixed Point Results of Single‐Valued Mapping for c‐Distance in Cone Metric Spaces
Authors: Fadail Zaid Mohammed , Bin Ahmad Abd Ghafur , Paunović Ljiljana
Published: September 2012

A new concept of the c‐distance in cone metric space has been introduced recently in 2011. The aim of this paper is to extend and generalize some fixed point results in literature for c‐distance in cone metric spaces by replacing the constants in contractive conditions with functions. Some supporting examples are given.
Evaluation of Safety and Protective Effect of Combined Extract ofCissampelos pareiraandAnethum graveolens(PM52) against Age-Related Cognitive Impairment
Authors: Thukham-mee Wipawee , Wattanathorn Jintanaporn
Published: September 2012

The present study aimed to determine acute toxicity, the protective effect, and underlying mechanism of PM52, a combined extract ofCissampelos pareiraandAnethum graveolens,against age-related cognitive impairment in animal model of age-related cognitive impairment. PM52 was determined as acute toxicity according to OECD guideline. Male Wistar rats, weighing 180–220 g, were orally given PM52 at doses of 2, 10, and 50 mg/kg at a period of 14 days before and 7 days after the bilateral administration of AF64A via intracerebroventricular route. All animals were assessed according to spatial memory, neuron density, MDA level, the activities of SOD, CAT, GSH-Px, and AChEI effect in hippocampus. It was found that all doses of PM52 could attenuate memory impairment and neurodegeneration in hippocampus. The possible mechanisms might occur via the suppression of AChE and the decreased oxidative stress in hippocampus. Therefore, our data suggest that PM52 may serve as food supplement to protect against age-related cognitive impairment such as mild cognitive impairment (MCI) and early phase of Alzheimer’s disease. However, further researches are still essential.
Social Determinants of Active Aging: Differences in Mortality and the Loss of Healthy Life between Different Income Levels among Older Japanese in the AGES Cohort Study
Authors: Hirai Hiroshi , Kondo Katsunori , Kawachi Ichiro
Published: September 2012

We examined the relationship between income, mortality, and loss of years of healthy life in a sample of older persons in Japan. We analyzed 22,829 persons aged 65 or older who were functionally independent at baseline as a part of the Aichi Gerontological Evaluation Study (AGES). Two outcome measures were adopted, mortality and loss of healthy life. Independent variables were income level and age. The occurrence of mortality and need for care during these 1,461 days were tracked. Cox regressions were used to calculate the hazard ratio for mortality and loss of healthy life by income level. We found that people with lower incomes were more likely than those with higher incomes to report worse health. For the overall sample, using the governmental administrative data, the hazard ratios of mortality and loss of healthy life-years comparing the lowest to the highest income level were 3.50 for men and 2.48 for women for mortality and 3.71 for men and 2.27 for women for loss of healthy life. When only those who responded to questions about income on the mail survey were included in the analysis, the relationships became weaker and lost statistical significance.
Tactile Modulation of Emotional Speech Samples
Authors: Salminen Katri , Surakka Veikko , Lylykangas Jani , Rantala Jussi , Ahmaniemi Teemu , Raisamo Roope , Trendafilov Dari , Kildal Johan
Published: September 2012

Traditionally only speech communicates emotions via mobile phone. However, in daily communication the sense of touch mediates emotional information during conversation. The present aim was to study if tactile stimulation affects emotional ratings of speech when measured with scales of pleasantness, arousal, approachability, and dominance. In the Experiment 1 participants rated speech-only and speech-tactile stimuli. The tactile signal mimicked the amplitude changes of the speech. In the Experiment 2 the aim was to study whether the way the tactile signal was produced affected the ratings. The tactile signal either mimicked the amplitude changes of the speech sample in question, or the amplitude changes of another speech sample. Also, concurrent static vibration was included. The results showed that the speech-tactile stimuli were rated as more arousing and dominant than the speech-only stimuli. The speech-only stimuli were rated as more approachable than the speech-tactile stimuli, but only in the Experiment 1. Variations in tactile stimulation also affected the ratings. When the tactile stimulation was static vibration the speech-tactile stimuli were rated as more arousing than when the concurrent tactile stimulation was mimicking speech samples. The results suggest that tactile stimulation offers new ways of modulating and enriching the interpretation of speech.
Prevalence of Overweight and Obesity among Adolescents in Seven Arab Countries: A Cross-Cultural Study
Authors: Musaiger Abdulrahman O. , Al-Mannai Mariam , Tayyem Reema , Al-Lalla Osama , Ali Essa Y. H. , Kalam Faiza , Benhamed Mofida M. , Saghir Sabri , Halahleh Ismail , Djoudi Zahra , Chirane Manel
Published: September 2012

Objective. The aim of this study was to find out the prevalence of overweight and obesity among adolescents in seven Arab countries using similar reference standard.Methods. A school-based cross-sectional study was carried out in seven cities in Arab countries, namely, Algeria, Jordan, Kuwait, Libya, Palestine, Syria, and United Arab Emirates. A multistage stratified random sampling technique was used. The total sample included was 4698 adolescents aged from 15 to 18 years (2240 males, 2458 females). The International Obesity Task Force (IOTF) reference standard was used to classify the adolescents as nonobese, overweight, and obese.Results. Among males, overweight was highest among Kuwaiti adolescents (25.6%), followed by Jordanian (21.6%), and Syrian (19.7%) adolescents. Among females, the highest prevalence of overweight was reported in Libyan adolescents (26.6%), followed by Kuwaiti (20.8%), and Syrian (19.7%) adolescents. As for obesity, Kuwaiti adolescents showed the highest prevalence of obesity for both males (34.8%) and females (20.6%).Conclusion. There is an urgent need to establish a plan of action to combat obesity in schoolchildren in these countries.
Synthesis of Silver Nanoparticles from the Aqueous Extract of Leaves of Ocimum sanctum for Enhanced Antibacterial Activity
Authors: Ramteke Charusheela , Chakrabarti Tapan , Sarangi Bijaya Ketan , Pandey Ram-Avatar
Published: September 2012

The field of nanotechnology is the most active area of research in modern materials science. Though there are many chemical as well as physical methods, green synthesis of nanomaterials is the most emerging method of synthesis. We report the synthesis of antibacterial silver nanoparticles (AgNPs) using leaf broth of medicinal herb, Ocimum sanctum (Tulsi). The synthesized AgNPs have been characterized by UV‐Vis spectroscopy, transmission electron microscopy (TEM), and X‐ray diffractometry. The mean particle of synthesized NPs was found to be 18 nm, as confirmed by TEM. The qualitative assessment of reducing potential of leaf extract has also been carried out which indicated presence of significant amount of reducing entities. FTIR analysis revealed that the AgNPs were stabilized by eugenols, terpenes, and other aromatic compounds present in the extract. Such AgNPs stabilized by Tulsi leaf extract were found to have enhanced antimicrobial activity against well‐known pathogenic strains, namely Staphylococcus aureus and E. coli.
Metabolic Associations of Reduced Proliferation and Oxidative Stress in Advanced Breast Cancer
Authors: Jerby Livnat , Wolf Lior , Denkert Carsten , Stein Gideon Y. , Hilvo Mika , Oresic Matej , Geiger Tamar , Ruppin Eytan
Published: September 2012

Aberrant metabolism is a hallmark of cancer, but whole metabolomic flux measurements remain scarce. To bridge this gap, we developed a novel metabolic phenotypic analysis (MPA) method that infers metabolic phenotypes based on the integration of transcriptomics or proteomics data within a human genome-scale metabolic model. MPA was applied to conduct the first genome-scale study of breast cancer metabolism based on the gene expression of a large cohort of clinical samples. The modeling correctly predicted cell lines' growth rates, tumor lipid levels, and amino acid biomarkers, outperforming extant metabolic modeling methods. Experimental validation was obtained in vitro. The analysis revealed a subtype-independent “go or grow” dichotomy in breast cancer, where proliferation rates decrease as tumors evolve metastatic capability. MPA also identified a stoichiometric tradeoff that links the observed reduction in proliferation rates to the growing need to detoxify reactive oxygen species. Finally, a fundamental stoichiometric tradeoff between serine and glutamine metabolism was found, presenting a novel hallmark of estrogen receptor (ER)+ versus ER− tumor metabolism. Together, our findings greatly extend insights into core metabolic aberrations and their impact in breast cancer. Cancer Res; 72(22); 5712–20. ©2012 AACR.
Relevance of Prehospital Stroke Code Activation for Acute Treatment Measures in Stroke Care: A Review
Authors: Baldereschi Marzia , Piccardi Benedetta , Di Carlo Antonio , Lucente Giuseppe , Guidetti Donata , Consoli Domenico , Provinciali Leandro , Toni Danilo , Sacchetti Maria Luisa , Polizzi Bianca Maria , Inzitari Domenico ,   for the Promotion and Implementation of Stroke Care in Italy Project – Working Group
Published: September 2012

Background: The use of emergency services with prehospital stroke assessment and early notification to the treatment hospital (stroke code) is a crucial determinant of delay time for acute stroke treatment. We reviewed and summarized the literature on prehospital stroke code system implementation. Methods: Two databases were explored (last update June 20, 2011) with 3 key words (stroke code, stroke prehospital management and stroke prehospital services). Inclusion criteria were: randomized and quasirandomized controlled trials, cohort and case-control studies, and hospital- and emergency-based registers, with no year or language restrictions. We examined the reference lists of all included articles. All potentially relevant reports and abstracts were transcribed into a specifically designed data abstraction form. Results: Only 19 of the 680 studies which were initially retrieved, published from 1999 to 2011, fulfilled our inclusion criteria. One clinical trial was identified. Large differences in stroke code procedures and study designs within and across countries prohibited the pooling of the data. Most studies were carried out in urban areas. Assuming the rate of tissue-plasminogen activator treatment as the performance measure, most studies report a significant increase in the rate of treatment (increase between 3.2 and 16%) with only 1 study not reporting any increase. Conclusions: Despite its limitations, this review suggests that the use of prehospital stroke code is an important intervention to improve the accessibility of the benefits of thrombolysis, especially when implemented together with educational campaigns to optimize the awareness and behavior of patients and bystanders.
Change in Cortical Vessel Signs on Susceptibility-Weighted Images after Full Recanalization in Hyperacute Ischemic Stroke
Authors: Baik Seung Kug , Choi Wonjin , Oh Se Jin , Park Kyung-Pil , Park Min-Gyu , Yang Tae Il , Jeong Hae Woong
Published: September 2012

Background: The cortical vessel signs (CVSs) on susceptibility-weighted images (SWIs) have been reported in patients with hyperacute ischemic stroke. We evaluated the change of this susceptibility sign on the immediate SWI after full recanalization and its clinical implications. Methods: Nineteen hyperacute ischemic stroke patients who had acute large artery occlusion and underwent post-recanalization SWI were enrolled in this study. The patients had ICA (internal carotid artery, 2 cases), M1 (M1 segment of middle cerebral artery, 7 cases), M2 (M2 segment of middle cerebral artery, 1 cases), T (intracranial ICA bifurcation, 2 cases), ICA/M1 (4 cases) and basilar artery (3 cases) occlusion on imaging studies before thrombolysis and they underwent immediate magnetic resonance imaging, including the SWI, after full recanalization. The recanalization status was evaluated using the thrombolysis in cerebral infarction (TICI) score before and after thrombolysis. The SWI images were evaluated for the presence of asymmetry of veins over the ischemic territory and this was correlated with the site of stenosis or occlusion. The veins in the ischemic territory were classified as ‘prominent’ if there were more numerous veins and/or large veins with a greater signal loss observed compared with the opposite normal hemisphere, ‘equal’ if there were no significant difference in appearance in both the cerebral hemispheres, and ‘less’ if the veins were decreased in the affected area as compared with that of the normal cortex. Baseline clinical parameters and clinical outcomes were reviewed. Results: The initial TICI grades were 0 in all cases. After thrombolysis, TICI grades were 3 in all cases. The pre-recanalization SWIs were obtained in 10 of 19 patients and all 10 showed prominent CVSs over the affected side, which disappeared on the post-recanalization SWI. On the post-recanalization SWI, the observed veins in the affected area were equal (10/19), less (5/19), and both equal and less (4/19). Patients with equal cortical veins in the affected area had small lesions on diffusion-weighted image (DWI) (10/19), while patients with less cortical veins had medium to large lesions on DWI (9/19). Conclusion: The prominent CVSs on SWI can be indicative of acute thromboembolic occlusion and its change immediately after recanalization can be used to reflect the metabolic status. After recanalization, the appearance of the equal CVS (return to normal) on SWI was associated with a favorable clinical outcome and infarction was avoided in our small series study.
Ticagrelor Versus Clopidogrel in Elderly Patients With Acute Coronary Syndromes
Authors: Husted Steen , James Stefan , Becker Richard C. , Horrow Jay , Katus Hugo , Storey Robert F. , Cannon Christopher P. , Heras Magda , Lopes Renato D. , Morais Joao , Mahaffey Kenneth W. , Bach Richard G. , Wojdyla Daniel , Wallentin Lars ,   for the PLATO study group
Published: September 2012

Background—

Elderly patients with acute coronary syndrome are at high risk of recurrent ischemic events and death, and for both antithrombotic therapy and catheter-based complications. This prespecified analysis investigates the effect and treatment-related complications of ticagrelor versus clopidogrel in elderly patients (≥75 years of age) with acute coronary syndrome compared with those <75 years of age.

Methods and Results—

The association between age and the primary composite outcome, as well as major bleeding were evaluated in the PLATelet inhibition and patient Outcomes (PLATO) trial using Cox proportional hazards. Similar models were used to evaluate the interaction of age with treatment effects. Hazard ratios were adjusted for baseline characteristics. The clinical benefit of ticagrelor over clopidogrel was not significantly different between patients aged ≥75 years of age (n=2878) and those <75 years of age (n=15 744) with respect to the composite of cardiovascular death, myocardial infarction, or stroke (interaction
P
=0.56), myocardial infarction (
P
=0.33), cardiovascular death (
P
=0.47), definite stent thrombosis (
P
=0.81), or all-cause mortality (
P
=0.76). No increase in PLATO-defined overall major bleeding with ticagrelor versus clopidogrel was observed in patients aged ≥75 years (hazard ratio, 1.02; 95% confidence interval, 0.82–1.27) or patients aged <75 years (hazard ratio, 1.04; 95% confidence interval, 0.94–1.15). Dyspnea and ventricular pauses were more common during ticagrelor than clopidogrel treatment, with no evidence of an age-by-treatment interaction.

Conclusions—

The significant clinical benefit and overall safety of ticagrelor compared with clopidogrel in acute coronary syndrome patients in the PLATO cohort were not found to depend on age.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00391872.
Transitions, Risks, and Actions in Coronary Events—Center for Outcomes Research and Education (TRACE-CORE)
Authors: Waring Molly E. , McManus Richard H. , Saczynski Jane S. , Anatchkova Milena D. , McManus David D. , Devereaux Randolph S. , Goldberg Robert J. , Allison Jeroan J. , Kiefe Catarina I. ,   for the TRACE-CORE Investigators
Published: September 2012

Background—

Cardiovascular disease continues to cause significant morbidity, mortality, and impaired quality of life, with unrealized health gains from the underuse of available evidence. The Transitions, Risks, and Actions in Coronary Events Center for Outcomes Research and Education (TRACE-CORE) aims to advance the science of acute coronary syndromes by examining the determinants and outcomes of the quality of transition from hospital to community and by quantifying the impact of potentially modifiable characteristics associated with decreased quality of life, rehospitalization, and mortality.

Methods and Results—

TRACE-CORE comprises a longitudinal multiracial cohort of patients hospitalized with acute coronary syndromes, 2 research projects, and development of a nucleus of early stage investigators. We are currently enrolling 2500 adults hospitalized for acute coronary syndromes at 6 hospitals in the northeastern and southeastern United States. We will follow these patients for 24 months after hospitalization through medical record abstraction and 5 patient interviews focusing on quality of life, cardiac events, rehospitalizations, mortality, and medical, behavioral, and psychosocial characteristics. The Transitions Project studies determinants of and disparities in outcomes of the quality of patients’ transition from hospital to community. Focusing on potentially modifiable factors, the Action Scores Project will develop and validate action scores to predict recurrent cardiac events, death, and quality of life, describe longitudinal variation in these scores, and develop a dashboard for patient and provider action on the basis of these scores.

Conclusions—

In TRACE-CORE, sound methodologic principles of observational studies converge with outcomes and effectiveness research approaches. We expect that our data, research infrastructure, and research projects will inform the development of novel secondary prevention approaches and underpin the careers of cardiovascular outcomes researchers.