bluuebunny/crossref_metadata_2025 huggingface dataset:
VEGF controls lung Th2 inflammation via the miR-1–Mpl (myeloproliferative leukemia virus oncogene)–P-selectin axis
Authors: Takyar Seyedtaghi , Vasavada Hema , Zhang Jian-ge , Ahangari Farida , Niu Naiqian , Liu Qing , Lee Chun Geun , Cohn Lauren , Elias Jack A.
Published: September 2013

Asthma, the prototypic Th2-mediated inflammatory disorder of the lung, is an emergent disease worldwide. Vascular endothelial growth factor (VEGF) is a critical regulator of pulmonary Th2 inflammation, but the underlying mechanism and the roles of microRNAs (miRNAs) in this process have not been defined. Here we show that lung-specific overexpression of VEGF decreases miR-1 expression in the lung, most prominently in the endothelium, and a similar down-regulation occurs in lung endothelium in Th2 inflammation models. Intranasal delivery of miR-1 inhibited inflammatory responses to ovalbumin, house dust mite, and IL-13 overexpression. Blocking VEGF inhibited Th2-mediated lung inflammation, and this was restored by antagonizing miR-1. Using mRNA arrays, Argonaute pull-down assays, luciferase expression assays, and mutational analysis, we identified Mpl as a direct target of miR-1 and showed that VEGF controls the expression of endothelial Mpl during Th2 inflammation via the regulation of miR-1. In vivo knockdown of Mpl inhibited Th2 inflammation and indirectly inhibited the expression of P-selectin in lung endothelium. These experiments define a novel VEGF–miR-1–Mpl–P-selectin effector pathway in lung Th2 inflammation and herald the utility of miR-1 and Mpl as potential therapeutic targets for asthma.
A Toxoplasma dense granule protein, GRA24, modulates the early immune response to infection by promoting a direct and sustained host p38 MAPK activation
Authors: Braun Laurence , Brenier-Pinchart Marie-Pierre , Yogavel Manickam , Curt-Varesano Aurélie , Curt-Bertini Rose-Laurence , Hussain Tahir , Kieffer-Jaquinod Sylvie , Coute Yohann , Pelloux Hervé , Tardieux Isabelle , Sharma Amit , Belrhali Hassan , Bougdour Alexandre , Hakimi Mohamed-Ali
Published: September 2013

Toxoplasma gondii, the causative agent of toxoplasmosis, is an obligate intracellular protozoan parasite that resides inside a parasitophorous vacuole. During infection, Toxoplasma actively remodels the transcriptome of its hosting cells with profound and coupled impact on the host immune response. We report that Toxoplasma secretes GRA24, a novel dense granule protein which traffics from the vacuole to the host cell nucleus. Once released into the host cell, GRA24 has the unique ability to trigger prolonged autophosphorylation and nuclear translocation of the host cell p38α MAP kinase. This noncanonical kinetics of p38α activation correlates with the up-regulation of the transcription factors Egr-1 and c-Fos and the correlated synthesis of key proinflammatory cytokines, including interleukin-12 and the chemokine MCP-1, both known to control early parasite replication in vivo. Remarkably, the GRA24–p38α complex is defined by peculiar structural features and uncovers a new regulatory signaling path distinct from the MAPK signaling cascade and otherwise commonly activated by stress-related stimuli or various intracellular microbes.
Phosphofructokinase deficiency impairs ATP generation, autophagy, and redox balance in rheumatoid arthritis T cells
Authors: Yang Zhen , Fujii Hiroshi , Mohan Shalini V. , Goronzy Jorg J. , Weyand Cornelia M.
Published: September 2013

In the HLA class II–associated autoimmune syndrome rheumatoid arthritis (RA), CD4 T cells are critical drivers of pathogenic immunity. We have explored the metabolic activity of RA T cells and its impact on cellular function and fate. Naive CD4 T cells from RA patients failed to metabolize equal amounts of glucose as age-matched control cells, generated less intracellular ATP, and were apoptosis-susceptible. The defect was attributed to insufficient induction of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), a regulatory and rate-limiting glycolytic enzyme known to cause the Warburg effect. Forced overexpression of PFKFB3 in RA T cells restored glycolytic flux and protected cells from excessive apoptosis. Hypoglycolytic RA T cells diverted glucose toward the pentose phosphate pathway, generated more NADPH, and consumed intracellular reactive oxygen species (ROS). PFKFB3 deficiency also constrained the ability of RA T cells to resort to autophagy as an alternative means to provide energy and biosynthetic precursor molecules. PFKFB3 silencing and overexpression identified a novel extraglycolytic role of the enzyme in autophagy regulation. In essence, T cells in RA patients, even those in a naive state, are metabolically reprogrammed with insufficient up-regulation of the glycolytic activator PFKFB3, rendering them energy-deprived, ROS- and autophagy-deficient, apoptosis-sensitive, and prone to undergo senescence.
Area laws in a many-body localized state and its implications for topological order
Authors: Bauer Bela , Nayak Chetan
Published: September 2013

The question whether Anderson insulators can persist to finite-strength interactions—a scenario dubbed many-body localization—has recently received a great deal of interest. The origin of such a many-body localized phase has been described as localization in Fock space, a picture we examine numerically. We then formulate a precise sense in which a single energy eigenstate of a Hamiltonian can be adiabatically connected to a state of a non-interacting Anderson insulator. We call such a state a many-body localized state and define a many-body localized phase as one in which almost all states are many-body localized states. We explore the possible consequences of this; the most striking is an area law for the entanglement entropy of almost all excited states in a many-body localized phase. We present the results of numerical calculations for a one-dimensional system of spinless fermions. Our results are consistent with an area law and, by implication, many-body localization for almost all states and almost all regions for weak enough interactions and strong disorder. However, there are rare regions and rare states with much larger entanglement entropies. Furthermore, we study the implications that many-body localization may have for topological phases and self-correcting quantum memories. We find that there are scenarios in which many-body localization can help to stabilize topological order at non-zero energy density, and we propose potentially useful criteria to confirm these scenarios.
Fish Oil (SMOFlipid) and Olive Oil Lipid (Clinoleic) in Very Preterm Neonates
Authors: Deshpande Girish , Simmer Karen , Deshmukh Mangesh , Mori Trevor A. , Croft Kevin D. , Kristensen Judy
Published: September 2013

Objectives:

Fat emulsions used in Australia for parenteral nutrition in preterm neonates have been based on either soybean oil or olive oil (OO). OO lipid Clinoleic has a high ratio of n‐6 to n‐3 fatty acids (9:1); this may not be ideal for long‐chain polyunsaturated fatty acids supply. Newly available SMOFlipid has an appropriate ratio of n‐6 to n‐3 fatty acids (2.5:1). SMOFlipid also contains OO (25%), coconut oil (30%), and soybean oil (30%). The aims of the study were to evaluate the safety of the SMOFlipid and to test the hypothesis that SMOFlipid would lead to increased omega‐3 long‐chain polyunsaturated fatty acid levels and reduced oxidative stress as compared with Clinoleic in preterm neonates (<30 weeks).

Methods:

Preterm neonates (23–30 weeks) were randomised to receive Clinoleic or SMOFlipid emulsion for 7 days. Investigators and outcome assessors were masked to allocation. Plasma F2‐isoprostanes (lipid peroxidation marker), red blood cell fatty acids, and vitamin E were measured before and after the study. Blood culture positive sepsis and growth were monitored for safety.

Results:

Thirty of 34 participants completed the study. Both emulsions were well tolerated without any adverse events. F2‐isoprostane levels were reduced in the SMOFlipid group as compared with baseline. Eicosapentanoic acid and vitamin E levels were significantly increased in the SMOFlipid group. Oleic acid and linoleic acid levels were increased in both groups. No significant differences were noted in poststudy docosahexaenoic acid levels in both groups despite higher levels of docosahexaenoic acid in SMOFlipid.

Conclusions:

SMOFlipid was safe, well tolerated, and showed beneficial effect in terms of reduction of oxidative stress by reducing lipid peroxidation levels in high‐risk preterm neonates.
Outcomes Following Infliximab Therapy for Pediatric Patients Hospitalized With Refractory Colitis–Predominant IBD
Authors: Falaiye Tolulope O. , Mitchell Keisha R. , Lu Zengqi , Saville Benjamin R. , Horst Sara N. , Moulton Dedrick E. , Schwartz David A. , Wilson Keith T. , Rosen Michael J.
Published: September 2013

Objectives:

Although randomized trials demonstrated the efficacy of infliximab for both pediatric Crohn disease and ulcerative colitis (UC), few patients in these studies exhibited colitis requiring hospitalization. The aims of this study were to determine the rate of subsequent infliximab failure and dose escalation in pediatric patients who started taking infliximab during hospitalization for colitis‐predominant IBD, and to identify potential predictors of these endpoints.

Methods:

This is a single‐center retrospective cohort study of patients admitted from 2005 to 2010 with Crohn colitis, UC, or IBD‐unspecified (IBD‐U) and initiated on infliximab.

Results:

We identified 29 patients (12 Crohn colitis, 15 UC, and 2 IBD‐U; median age 14 years) with a median follow‐up of 923 days. Eighteen patients (62%) required infliximab dose escalation (increased dose or decreased infusion interval). Infliximab failure occurred in 18 patients (62%) because of ineffectiveness in 12 (67%) and adverse reactions in 6 (33%). Twelve patients (41%) underwent colectomy. Subsequent need for infliximab dose escalation was associated with lower body mass index z score (P = 0.01), lower serum albumin (P = 0.03), and higher erythrocyte sedimentation rate (ESR) (P = 0.002) at baseline. ESR predicted subsequent infliximab dose escalation with an area under the curve of 0.89 (95% confidence interval [CI] 0.72–1.00) and a sensitivity and specificity at a cutoff of 38 mm/hour of 0.79 (95% CI 0.49–0.95) and 0.88 (95% CI 0.47–0.99), respectively.

Conclusions:

Most hospitalized pediatric patients with colitis treated with infliximab require early‐dose escalation and fail the drug long term. Low body mass index and albumin and high ESR, may identify patients who would benefit from a higher infliximab starting dose.
Climate sensitivity, sea level and atmospheric carbon dioxide
Authors: Hansen James , Sato Makiko , Russell Gary , Kharecha Pushker
Published: September 2013

Cenozoic temperature, sea level and CO
2
covariations provide insights into climate sensitivity to external forcings and sea-level sensitivity to climate change. Climate sensitivity depends on the initial climate state, but potentially can be accurately inferred from precise palaeoclimate data. Pleistocene climate oscillations yield a fast-feedback climate sensitivity of 3±1
°
C for a 4 W m
−2
CO
2
forcing if Holocene warming relative to the Last Glacial Maximum (LGM) is used as calibration, but the error (uncertainty) is substantial and partly subjective because of poorly defined LGM global temperature and possible human influences in the Holocene. Glacial-to-interglacial climate change leading to the prior (Eemian) interglacial is less ambiguous and implies a sensitivity in the upper part of the above range, i.e. 3–4
°
C for a 4 W m
−2
CO
2
forcing. Slow feedbacks, especially change of ice sheet size and atmospheric CO
2
, amplify the total Earth system sensitivity by an amount that depends on the time scale considered. Ice sheet response time is poorly defined, but we show that the slow response and hysteresis in prevailing ice sheet models are exaggerated. We use a global model, simplified to essential processes, to investigate state dependence of climate sensitivity, finding an increased sensitivity towards warmer climates, as low cloud cover is diminished and increased water vapour elevates the tropopause. Burning all fossil fuels, we conclude, would make most of the planet uninhabitable by humans, thus calling into question strategies that emphasize adaptation to climate change.
Sensitivity of the Palaeocene–Eocene Thermal Maximum climate to cloud properties
Authors: Kiehl Jeffrey T. , Shields Christine A.
Published: September 2013

The Palaeocene–Eocene Thermal Maximum (PETM) was a significant global warming event in the Earth's history (approx. 55 Ma). The cause for this warming event has been linked to increases in greenhouse gases, specifically carbon dioxide and methane. This rapid warming took place in the presence of the existing Early Eocene warm climate. Given that projected business-as-usual levels of atmospheric carbon dioxide reach concentrations of 800–1100 ppmv by 2100, it is of interest to study past climates where atmospheric carbon dioxide was higher than present. This is especially the case given the difficulty of climate models in simulating past warm climates. This study explores the sensitivity of the simulated pre-PETM and PETM periods to change in cloud condensation nuclei (CCN) and microphysical properties of liquid water clouds. Assuming lower levels of CCN for both of these periods leads to significant warming, especially at high latitudes. The study indicates that past differences in cloud properties may be an important factor in accurately simulating past warm climates. Importantly, additional shortwave warming from such a mechanism would imply lower required atmospheric CO
2
concentrations for simulated surface temperatures to be in reasonable agreement with proxy data for the Eocene.
How warm was the last interglacial? New model–data comparisons
Authors: Otto-Bliesner Bette L. , Rosenbloom Nan , Stone Emma J. , McKay Nicholas P. , Lunt Daniel J. , Brady Esther C. , Overpeck Jonathan T.
Published: September 2013

A Community Climate System Model, Version 3 (CCSM3) simulation for 125 ka during the Last Interglacial (LIG) is compared to two recent proxy reconstructions to evaluate surface temperature changes from modern times. The dominant forcing change from modern, the orbital forcing, modified the incoming solar insolation at the top of the atmosphere, resulting in large positive anomalies in boreal summer. Greenhouse gas concentrations are similar to those of the pre-industrial (PI) Holocene. CCSM3 simulates an enhanced seasonal cycle over the Northern Hemisphere continents with warming most developed during boreal summer. In addition, year-round warming over the North Atlantic is associated with a seasonal memory of sea ice retreat in CCSM3, which extends the effects of positive summer insolation anomalies on the high-latitude oceans to winter months. The simulated Arctic terrestrial annual warming, though, is much less than the observational evidence, suggesting either missing feedbacks in the simulation and/or interpretation of the proxies. Over Antarctica, CCSM3 cannot reproduce the large LIG warming recorded by the Antarctic ice cores, even with simulations designed to consider observed evidence of early LIG warmth in Southern Ocean and Antarctica records and the possible disintegration of the West Antarctic Ice Sheet. Comparisons with a HadCM3 simulation indicate that sea ice is important for understanding model polar responses. Overall, the models simulate little global annual surface temperature change, while the proxy reconstructions suggest a global annual warming at LIG (as compared to the PI Holocene) of approximately 1
°
C, though with possible spatial sampling biases. The CCSM3 SRES B1 (low scenario) future projections suggest high-latitude warmth similar to that reconstructed for the LIG may be exceeded before the end of this century.
The Early Eocene equable climate problem: can perturbations of climate model parameters identify possible solutions?
Authors: Sagoo Navjit , Valdes Paul , Flecker Rachel , Gregoire Lauren J.
Published: September 2013

Geological data for the Early Eocene (56–47.8 Ma) indicate extensive global warming, with very warm temperatures at both poles. However, despite numerous attempts to simulate this warmth, there are remarkable data–model differences in the prediction of these polar surface temperatures, resulting in the so-called ‘equable climate problem’. In this paper, for the first time an ensemble with a perturbed climate-sensitive model parameters approach has been applied to modelling the Early Eocene climate. We performed more than 100 simulations with perturbed physics parameters, and identified two simulations that have an optimal fit with the proxy data. We have simulated the warmth of the Early Eocene at 560 ppmv CO2, which is a much lower CO2level than many other models. We investigate the changes in atmospheric circulation, cloud properties and ocean circulation that are common to these simulations and how they differ from the remaining simulations in order to understand what mechanisms contribute to the polar warming. The parameter set from one of the optimal Early Eocene simulations also produces a favourable fit for the last glacial maximum boundary climate and outperforms the control parameter set for the present day. Although this does not ‘prove’ that this model is correct, it is very encouraging that there is a parameter set that creates a climate model able to simulate well very different palaeoclimates and the present-day climate. Interestingly, to achieve the great warmth of the Early Eocene this version of the model does not have a strong future climate change Charney climate sensitivity. It produces a Charney climate sensitivity of 2.7°C, whereas the mean value of the 18 models in the IPCC Fourth Assessment Report (AR4) is 3.26°C±0.69°C. Thus, this value is within the range and below the mean of the models included in the AR4.
Growth factor signaling and memory formation: temporal and spatial integration of a molecular network
Authors: Kopec Ashley M. , Carew Thomas J.
Published: September 2013

Growth factor (GF) signaling is critically important for developmental plasticity. It also plays a crucial role in adult plasticity, such as that required for memory formation. Although different GFs interact with receptors containing distinct types of kinase domains, they typically signal through converging intracellular cascades (e.g., Ras–MEK–MAPK) to mediate overlapping functional endpoints. Several GFs have been implicated in memory formation, but due to a high level of convergent signaling, the unique contributions of individual GFs as well as the interactions between GF signaling cascades during the induction of memory is not well known. In this review, we highlight the unique roles of specific GFs in dendritic plasticity, and discuss the spatial and temporal profiles of different GFs during memory formation. Collectively, the data suggest that the roles of GF signaling in long-lasting behavioral and structural plasticity may be best viewed as interactive components in a complex molecular network.
Calcium carbonate microparticle templates using a PHOS-b-PMAA double hydrophilic copolymer
Authors: Mihai Marcela , Mountrichas Grigoris , Pispas Stergios , Stoica Iuliana , Aflori Magdalena , Auf der Landwehr Maria , Neda Ion , Schwarz Simona
Published: September 2013

The crystallization characteristics of calcium carbonate microparticles grown from supersaturated aqueous solutions in the presence of a double hydrophilic block copolymer poly(p-hydroxystyrene-b-methacrylic acid), PHOS-b-PMAA, have been investigated. The studies aim to highlight both the possibilities and the limitations of CaCO3/PHOS-b-PMAA microparticle formation under different relative inorganic/polymer ratio conditions, varying the initial solution supersaturation or the polymer concentration. Scanning electron microscopy and atomic force microscopy were used to provide high-resolution images of particles and thereby information on the particle morphology, while X-ray diffraction analysis was used to determine the polymorph type and crystallite characteristics. The presence of the polymer in the composite particles was shown by thermogravimetric, particle charge density and zeta potential analysis. The polymer-induced sensitivity of the new composites to environmental pH variations has been followed by streaming potential variation.
Determination of fluctuations in local symmetry and measurement by convergent beam electron diffraction: applications to a relaxor-based ferroelectric crystal after thermal annealing
Authors: Kim Kyou-Hyun , Payne David A. , Zuo Jian Min
Published: September 2013

Single crystals of Pb(Mg1/3Nb2/3)O3–31%PbTiO3(PMN–31%PT) are known for their complex domain structures at the nanometre scale. While their average symmetry has been studied by X-ray, neutron and electron diffraction methods, there is little knowledge about variations in symmetry at the local scale. Here, direct evidence is provided for the volume dependence and spatial dependence of symmetry fluctuations by using quantitative convergent beam electron diffraction and energy dispersive X-ray spectroscopy. Fluctuations in symmetry were determined by using different electron beam probe sizes ranging from ∼2 to 25 nm from a crystal ∼62 nm thick. The symmetry of PMN–31%PT was found to increase linearly as the average volume increased, and the local symmetry fluctuated from one location to another at the nanoscale. Energy dispersive X-ray spectroscopy indicates that chemical fluctuations are significant when the probe size decreases to ∼2 nm. The symmetry fluctuation is attributed to locally varying composition-dependent ionic displacements and spontaneous polarization.
Multiple twinning in pure hexagonal close-packed titanium
Authors: Bao Lei , Zhang Yudong , Schuman Christophe , Lecomte Jean-Sébastien , Philippe Marie-Jeanne , Zhao Xiang , Esling Claude
Published: September 2013

Commercial pure titanium (T40) was deformed in channel die compression by means of the split-sample technique in order to study multiple twinning. Particular attention was paid to the twin variant presentation and selection during multiple twinning. All possible misorientations, corresponding to the multiple twins arising from the combination of the {1 1 {\overline 2} 2} compression (C) twin, the {1 0 {\overline 1} 2} tension twin (T1) and the {1 1 {\overline 2} 1} tension twin (T2), were calculated with respect to the crystal basis of the matrix grain. All the multiple twin variants are partitioned into ten classes with the same crystallographically equivalent misorientation angle and axis. However, when the influence of twinning order is taken into account, the multiple twin variants are partitioned into 15 classes. Experimental results prove that the selection of twin variants (primary and secondary) is mainly governed by their macroscopic Schmid factor (SF). The normalized SF is more efficient at predicting variant selection. A twin formed in one grain can activate another twin in a neighbouring grain, provided that the angle between the two twinning planes does not exceed 20°.
Banking on Food: The State of Food Banks in High‐income Countries
Authors: Gentilini Ugo
Published: September 2013

Food banks provide food to charities and other grassroots organisations for supporting vulnerable populations. As such, they tend to complement more institutionalised, state‐provided safety net programmes. This paper is a first attempt to estimate the total number of people supported by food banks in high‐income countries (HICs). The analysis shows that nearly 60 million people turn annually to food banks in ‘rich’ nations – that is, a level similar to the entire population of France or Italy and representing about 7.2 per cent of the HIC population. Such level could be considered a conservative estimate. This scenario suggests a number of implications for social protection policy, as well as opening new frontiers for food assistance practice, partnerships and applied research. The paper concludes that (i) the need for food banks will likely stay high or even increase further in the coming future; (ii) food bank models, activities and operations require further review, appraisal and documentation; (iii) debates should not confuse responses to and causes of poverty, food insecurity and socio‐economic marginalisation; and (iv) the nature, context and objectives of food assistance in advanced economies are different from those in developing countries, although scope for galvanising cooperation exists.
Sex Work and its Linkages with Informal Labour Markets in India: Findings from the First Pan‐India Survey of Female Sex Workers
Authors: Sahni Rohini , Shankar V. Kalyan
Published: September 2013

Based on the results of the First Pan India Survey of Female Sex Workers (n=3000), this paper positions sex work within the broader spectrum of informal labour markets that women engage with in India. It puts forth an important dimension missing so far in sex work studies in India – of sex workers with prior or simultaneous labour market work experience. Informal labour markets act as important sites/junctures linking poverty with sex work. For a substantial proportion of respondents, sex work was not their first experience of paid work. In the face of poverty and an early quest for livelihoods, they were pushed into informal labour activities, characterised by low, sticky wages and imminent possibilities of abuse. Placed in this context, their later entry into sex work emerges with a strong economic rationale and agency, as a deliberate, calculated choice offering higher incomes.
The lateral reticular nucleus: a precerebellar centre providing the cerebellum with overview and integration of motor functions at systems level. A new hypothesis
Authors: Alstermark Bror , Ekerot Carl‐Fredrik
Published: September 2013

Abstract  The lateral reticular nucleus (LRN) is a major precerebellar centre of mossy fibre information to the cerebellum from the spinal cord that is distinct from the direct spinocerebellar paths. The LRN has traditionally been considered to provide the cerebellum with segregated information from several spinal systems controlling posture, reaching, grasping, locomotion, scratching and respiration. However, results are presented that show extensive convergence on a majority of LRN neurons from spinal systems. We propose a new hypothesis suggesting that the LRN may use extensive convergence from the different input systems to provide overview and integration of linked motor components to the cerebellum. This integrated information is sent in parallel with the segregated information from the individual systems to the cerebellum that finally may compare the activity and make necessary adjustments of various motor behaviours.
The emergence of subcellular pacemaker sites for calcium waves and oscillations
Authors: Nivala Michael , Ko Christopher Y. , Nivala Melissa , Weiss James N. , Qu Zhilin
Published: September 2013

Key points

Calcium (Ca2+) is fundamental to biological cell function, and Ca2+ waves generating oscillatory Ca2+ signals are widely observed in many cell types.

Some experimental studies have shown that Ca2+ waves initiate from random locations within the cell, while other studies have shown that waves occur repetitively from preferred locations (pacemaker sites).

In both ventricular myocyte experiments and computer simulations of a heterogeneous model of coupled Ca2+ release units (CRUs), we show that Ca2+ waves occur randomly in space and time when the Ca2+ level is low, but as the Ca2+ level increases, waves occur repetitively from the same sites.

Ca2+ waves are self‐organized dynamics of the CRU network, and the wave frequency strongly depends on CRU coupling.

Using these results, we develop a theory for the entrainment of random oscillators, which provides a unified explanation for the experimental and computational observations.

Abstract  Calcium (Ca2+) waves generating oscillatory Ca2+ signals are widely observed in biological cells. Experimental studies have shown that under certain conditions, initiation of Ca2+ waves is random in space and time, while under other conditions, waves occur repetitively from preferred locations (pacemaker sites) from which they entrain the whole cell. In this study, we use computer simulations to investigate the self‐organization of Ca2+ sparks into pacemaker sites generating Ca2+ oscillations. In both ventricular myocyte experiments and computer simulations of a heterogeneous Ca2+ release unit (CRU) network model, we show that Ca2+ waves occur randomly in space and time when the Ca2+ level is low, but as the Ca2+ level increases, waves occur repetitively from the same sites. Our analysis indicates that this transition to entrainment can be attributed to the fact that random Ca2+ sparks self‐organize into Ca2+ oscillations differently at low and high Ca2+ levels. At low Ca2+, the whole cell Ca2+ oscillation frequency of the coupled CRU system is much slower than that of an isolated single CRU. Compared to a single CRU, the distribution of interspike intervals (ISIs) of the coupled CRU network exhibits a greater variation, and its ISI distribution is asymmetric with respect to the peak, exhibiting a fat tail. At high Ca2+, however, the coupled CRU network has a faster frequency and lesser ISI variation compared to an individual CRU. The ISI distribution of the coupled network no longer exhibits a fat tail and is well‐approximated by a Gaussian distribution. This same Ca2+ oscillation behaviour can also be achieved by varying the number of ryanodine receptors per CRU or the distance between CRUs. Using these results, we develop a theory for the entrainment of random oscillators which provides a unified explanation for the experimental observations underlying the emergence of pacemaker sites and Ca2+ oscillations.
Damping and Inertia Coefficients for Two End Sealed Squeeze Film Dampers With a Central Groove: Measurements and Predictions
Authors: San Andrés Luis , Seshagiri Sanjeev
Published: September 2013

Aircraft engine rotors, invariably supported on rolling element bearings with little damping, are particularly sensitive to rotor imbalance and sudden maneuver loads. Most engines incorporate squeeze film dampers (SFDs) as a means to dissipate mechanical energy from rotor motions and to ensure system stability. The paper experimentally quantifies the dynamic forced performance of two end sealed SFDs with dimensions and an operating envelope akin to those in actual jet engine applications. The current experimental results complement and extend prior research conducted with open ends SFDs (San Andrés, 2012, “Damping and Inertia Coefficients for Two Open Ends Squeeze Film Dampers With a Central Groove: Measurements and Predictions,” ASME J. Eng. Gas Turbines Power, 134, p. 102506). In the tests, two journals make for two SFD configurations, both with a diameter D = 127 mm and nominal radial film clearance c = 0.127 mm. One short length damper has film lands with extent L = 12.7 mm, while the other has 25.4 mm ( = 2L) land lengths. A central groove of length LG = L and depth at ¾ L separates the film lands. A light viscosity lubricant is supplied into the central groove via three orifices, 120 deg apart, and then flows through the film lands whose ends are sealed with tight piston rings. The oil pushes through the piston rings to discharge at ambient pressure. In the tests, a static load device pulls the damper structure to increasing eccentricities (maximum 0.38c) and external shakers exert single-frequency loads 50–250 Hz, inducing circular orbits with amplitudes equaling ∼5% of the film clearance. The lubricant feed and groove pressures and flow rates through the top and bottom film lands are recorded to determine the flow resistances through the film lands and the end seals. Measured dynamic pressures in the central groove are as large as those in the film lands, thus demonstrating a strong flow interaction, further intensified by the piston ring end seals which are effective in preventing side leakage. Dynamic pressures and reaction loads are substantially higher than those recorded with the open ends dampers. Comparisons to test results for two identical damper configurations but open ended (San Andrés, 2012, “Damping and Inertia Coefficients for Two Open Ends Squeeze Film Dampers With a Central Groove: Measurements and Predictions,” ASME J. Eng. Gas Turbines Power, 134, p. 102506) demonstrate at least a threefold increase in direct damping coefficients and no less than a double increment in added mass coefficients. Predictions from a physics-based model that includes the central groove, the lubricant feed holes, and the end seals' flow conductances are in agreement with the test results for the short length damper. For the long damper, the predicted damping coefficients are in good agreement with the measurements, while the added masses are under-predicted by ∼25%.
Assessment of a Gas Turbine NOx Reduction Potential Based on a Spatiotemporal Unmixedness Parameter
Authors: Dederichs Stefan , Zarzalis Nikolaos , Habisreuther Peter , Beck Christian , Prade Bernd , Krebs Werner
Published: September 2013

The paper presents a one-dimensional approach to assess the reduction potential of NOx emissions for lean premixed gas turbine combustion systems. NOx emissions from these systems are known to be mainly caused by high temperatures, not only from an averaged perspective but especially related to poor mixing quality of fuel and air. The method separates the NOx chemistry in the flame front zone and the postflame zone (slow reaction). A one-dimensional treatment enables the use of detailed chemistry. A lookup table parameterized by reaction progress and equivalence ratio is used to improve the computational efficiency. The influence of mixing quality is taken into account by a probability density function of the fuel element–based equivalence ratio, which itself translates into a temperature distribution. Hence, the NOx source terms are a function of reaction progress and equivalence ratio. The reaction progress is considered by means of the two-zone approach. Based on unsteady computational fluid dynamics (CFD) data, the evolution of the probability density function with residence time has been analyzed. Two types of definitions of an unmixedness quantity are considered. One definition accounts for spatial as well as temporal fluctuations, and the other is based on the mean spatial distribution. They are determined at the location of the flame front. The paper presents a comparison of the modeled results with experimental data. A validation and application have shown very good quantitative and qualitative agreement with the measurements. The comparison of the unmixedness definitions has proven the necessity of unsteady simulations. A general emissions-unmixedness correlation can be derived for a given combustion system.
Alternative Microturbine Fuels Feasibility Study Through Thermal Stability, Material Compatibility, and Engine Testing
Authors: Arias Quintero Sergio , Schmitt Joshua , Blair Richard , Kapat Jayanta
Published: September 2013

Historically, gas turbine fuels have been procured based on availability and low cost criteria. However,in the past few decades, with the growing concern over the negative environmental impacts produced by emissions, alternative fuels have been developed and tested under the objective of reducing such negative effects. The physical properties and broad chemical composition of fuels, including trace elements, may result in engine performance issues found only after extensive operation. This, in turn, results in higher maintenance and operation costs. This paper studies the feasibility of several renewable fuels for microturbine application, identifying key relationships between the physical and chemical properties, thermal stability, materials compatibility, and turbine performance.
Automatic detection of microcalcifications in breast ultrasound
Authors: Chang Ruey‐Feng , Hou Yu‐Ling , Huang Chiun‐Sheng , Chen Jeon‐Hor , Chang Jung Min , Moon Woo Kyung
Published: September 2013

Purpose:

In an ultrasound (US) image, the presence of microcalcifications within breast lesions is an important indicator of malignancy. The purpose of this study was to develop a novel automatic detection system to find microcalcifications inside a breast lesion using an US image.

Methods:

Breast US images from 103 cases with microcalcifications were obtained using an US system with a 6–14 MHz transducer, and 585 microcalcification foci marked on 103 breast US images by a radiologist were used as the ground truth. After segmentation of the lesion contour using the level set method, the microcalcification candidates inside the lesion were found using adaptive speckle reduction and top hat filters. Then, three criteria were used to identify the real microcalcifications, including the mean, single point, and brightness criteria.

Results:

The proposed method revealed microcalcifications within the lesions in all 103 cases. The sensitivity and the false positive (FP) rate for the detection of microcalcification foci were 80.3% (470/585) and 3.1 per case, respectively. The sensitivities and FP rates for the benign and malignant cases were 79.2% (243/307) with a FP rate of 3.5 and 81.7% (227/278) with a FP rate of 2.6, respectively.

Conclusions:

The authors’ proposed method has the potential to provide a tool to help physicians detect microcalcifications within breast lesions.
How to Use a Candle to Study Sound Waves
Authors: Simeão Carvalho P. , Briosa E. , Rodrigues M. , Pereira C. , Ataíde M.
Published: September 2013

It is well known that sound waves in air are longitudinal waves. Although teachers use analogies such as compressing horizontal springs to demonstrate what longitudinal waves look like, students still present some difficulty in understanding that (1) sound waves correspond to oscillations of air particles, and (2) there is no “air flow” (transport of particles) in sound waves.1,2 These difficulties arise from the impossibility to actually “see” air particles moving, and from the common sense idea that free particles always have translational motion.
Big Pile or Small Pile?
Authors: Branca Mario , Quidacciolu Rossana G. , Soletta Isabella
Published: September 2013

The construction of a voltaic pile (battery) is a simple laboratory activity that commemorates the invention of this important device and is of great help in teaching physics. The voltaic pile is often seen as a scientific toy, with the “pile” being constructed from fruit. These toys use some strips of copper and zinc inserted in a piece of fruit to produce a low-intensity electrical current to power a digital device. In a voltaic pile of this type, the zinc acts as an anode while the copper acts as a cathode. The reduction reaction [i.e.,2H+(aq)+2e⇋H2(g)] occurs on the copper (the cathode). The two electrons that are needed for the reduction are taken from the metal (copper), which remains positively charged, while the anode is the zinc, which is oxidized through the reaction Zn∘(m)⇋Zn+2(aq)+2e, and the two electrons remain on the metal, which is negatively charged. If the two pieces of metal are connected by an external conductor, electrons flow from the zinc to the copper. The electromotive force of this system is about 0.76 V, which is the reduction potential of zinc, as can be found in the table of standard reduction potentials.1
Segmented Hoop as a Physical Pendulum
Authors: Layton William , Rodriguez Nuria
Published: September 2013

An interesting demonstration with a surprising result is to suspend a hoop from a point near its edge and set it swinging in a vertical plane as a pendulum. If a simple pendulum of length equal to the diameter of the hoop is set oscillating at the same time, the two will have nearly the same period. However, the real surprise is if the pendulum is segmented horizontally (as illustrated in Fig. 1) into smaller pieces that are symmetrical about the point of suspension, each smaller segment will also have the same period. Constructing such a demonstration can be difficult, but thanks to a suggestion from a fellow physics teacher1 a dissectible hula hoop can be purchased that serves well in this demonstration.2 A setup that has been repeated many times at various physics teacher meetings in Southern California is illustrated below.
Galilean Moons, Kepler's Third Law, and the Mass of Jupiter
Authors: Bates Alan
Published: September 2013

Simulations of physical systems are widely available online, with no cost, and are ready to be used in our classrooms.1,2 Such simulations offer an accessible tool that can be used for a range of interactive learning activities. The Jovian Moons Applet2 allows the user to track the position of Jupiter's four Galilean moons with a variety of viewing options. For this activity, data are obtained from the orbital period and orbital radii charts. Earlier experiments have used telescopes to capture the orbital motion of the Galilean moons,3 although observation of astronomical events and the measurement of quantities may be difficult to achieve due to a combination of cost, training, and observing conditions. The applet allows a suitable set of data to be generated and data analysis that verifies Kepler's third law of planetary motion, which leads to a calculated value for the mass of Jupiter.
Erie Canal Technology: Stump Pullers
Authors: Greenslade Thomas B.
Published: September 2013

Many years ago I saw a picture of a huge set of wheels that was used to remove tree stumps during the construction of the Erie Canal (1817–1825) and was intrigued by its use of leverage, mechanical advantage, and torque. Figure 1 is a scale model of the device based on my memory of the (lost) picture and published accounts.1
Brd4 Shields Chromatin from ATM Kinase Signaling Storms
Authors: Choi Serah , Bakkenist Christopher J.
Published: September 2013

New studies identify chromatin-binding proteins that modulate ATM signaling in response to DNA damage.
High-Temperature Mating Success
Authors: VanHook Annalisa M.
Published: September 2013

A peptide produced in pistils promotes pollen performance and mitochondrial activity at high temperature.
Cutting Off EMT at the Pass
Authors: Ferrarelli Leslie K.
Published: September 2013

Critical signal transduction components in the epithelial-to-mesenchymal transition of breast and brain cancer offer new clinical targets.
Antiplasmodial Activity and Mechanism of Action of RSM-932A, a Promising Synergistic Inhibitor of Plasmodium falciparum Choline Kinase
Authors: Zimmerman Tahl , Moneriz Carlos , Diez Amalia , Bautista José Manuel , Gómez del Pulgar Teresa , Cebrián Arancha , Lacal Juan Carlos
Published: September 2013

We have investigated the mechanism of action of inhibition of the choline kinase ofP. falciparum(p.f.-ChoK) by two inhibitors of the human ChoKα, MN58b and RSM-932A, which have previously been shown to be potent antitumoral agents. The efficacy of these inhibitors againstp.f.-ChoK is investigated using enzymatic andin vitroassays. While MN58b may enter the choline/phosphocholine binding site, RSM-932A appears to have an altogether novel mechanism of inhibition and is synergistic with respect to both choline and ATP. A model of inhibition for RSM-932A in which this inhibitor trapsp.f.-ChoK in a phosphorylated intermediate state blocking phosphate transfer to choline is presented. Importantly, MN58b and RSM-932A havein vitroinhibitory activity in the low nanomolar range and are equally effective against chloroquine-sensitive and chloroquine-resistant strains. RSM-932A and MN58b significantly reduced parasitemia and induced the accumulation of trophozoites and schizonts, blocking intraerythrocytic development and interfering with parasite egress or invasion, suggesting a delay of the parasite maturation stage. The present data provide two new potent structures for the development of antimalarial compounds and validatep.f.-ChoK as an accessible drug target against the parasite.
Comparative Evaluation of Serotonin Toxicity among Veterans Affairs Patients Receiving Linezolid and Vancomycin
Authors: Lodise T. P. , Patel N. , Rivera A. , Tristani L. , Lazariu V. , Vandewall H. , McNutt L. A.
Published: September 2013

Despite the theoretical risk of serotonin toxicity (ST) with linezolid, “real-world” clinical evaluations of the risk of ST in patients receiving linezolid have been limited to case reports and noncomparator studies. An observational, matched-cohort study was conducted to evaluate the risk of ST among hospitalized patients who received linezolid or vancomycin at the Upstate New York Veterans Affairs Healthcare Network (Veterans Integrated Service Network 2 [VISN-2]). Matching criteria included VISN-2 hospital, hospital ward, prior hospital length of stay, age, and baseline platelet counts. The patients' electronic medical records were evaluated for symptoms consistent with ST and the Hunter serotonin toxicity criteria (HSTC) using an intensive, natural word search algorithm. The study included 251 matched pairs. Demographics and comorbidities were similar between groups. Over half of the study population received at least one concurrent medication with serotonergic activity. Receipt of agents with serotonergic activity was more pronounced in the vancomycin group, and the higher frequency was due to concomitant antihistamine and antiemetic use. Antidepressant use, including selective serotonin reuptake inhibitors (SSRIs), was similar between groups. No patients in either group were found to meet the criteria using the word search algorithm for ST. Fewer linezolid patients than vancomycin patients met the HSTC overall (3.2% versus 8.8%) and when stratified by receipt of a concurrent serotonergic agent (4.3% versus 12.4%). Of the patients meeting the HSTC, most had past or present comorbidities that may have contributed to or overlapped the HSTC. This study of hospitalized patients revealed comparably low frequencies of adverse events potentially related to ST among patients who received linezolid or vancomycin.
The Clonal Distribution and Diversity of Extraintestinal Escherichia coli Isolates Vary According to Patient Characteristics
Authors: Banerjee Ritu , Johnston Brian , Lohse Christine , Chattopadhyay Sujay , Tchesnokova Veronika , Sokurenko Evgeni V. , Johnson James R.
Published: September 2013

The clonal distribution of
Escherichia coli
across an unselected population in the current era of widespread antimicrobial resistance is incompletely defined. In this study, we used a newly described clonal typing strategy based on sequencing of
fum

C

and
fim

H

(i.e., CH typing) to infer multilocus sequence types (STs) for 299 consecutive, nonduplicate extraintestinal
E. coli
isolates from all cultures submitted to Olmsted County, MN, laboratories in February and March 2011 and then compared STs with epidemiological data. Forty-seven different STs were identified, most commonly ST131 (27%), ST95 (11%), ST73 (8%), ST127 (6%), and ST69 (5%). Isolates from these five STs comprised two-thirds of health care-associated (HA) isolates but only half of community-associated (CA) isolates. ST131 was represented overwhelmingly (88%) by a single recently expanded H30 subclone, which was the most extensively antimicrobial-resistant subclone overall and was especially predominant in HA infections and among adults >50 years old. In contrast, among patients 11 to 50 years old, ST69, -95, and -73 were more common. Because of the preponderance of the H30 subclone of ST131, ST diversity was lower among HA than CA isolates, and among antimicrobial-resistant than antimicrobial-susceptible isolates, which otherwise had similar ST distributions. In conclusion, in this U.S. Midwest region, the distribution and diversity of STs among extraintestinal
E. coli
clinical isolates vary by patient age, type of infection, and resistance phenotype. ST131 predominates among young children and the elderly, HA infections, and antimicrobial-resistant isolates, whereas other well-known pathogenic lineages are more common among adolescents and young adults, CA infections, and antimicrobial-susceptible isolates.