Cecum lymph node dendritic cells harbor slow-growing bacteria phenotypically tolerant to antibiotic treatment.

In vivo, antibiotics are often much less efficient than ex vivo and relapses can occur. The reasons for poor in vivo activity are still not completely understood. We have studied the fluoroquinolone antibiotic ciprofloxacin in an animal model for complicated Salmonellosis. High-dose ciprofloxacin treatment efficiently reduced pathogen loads in feces and most organs. However, the cecum draining lymph node (cLN), the gut tissue, and the spleen retained surviving bacteria. In cLN, approximately 10%-20% of the bacteria remained viable. These phenotypically tolerant bacteria lodged mostly within CD103⁺CX₃CR1⁻CD11c⁺ dendritic cells, remained genetically susceptible to ciprofloxacin, were sufficient to reinitiate infection after the end of the therapy, and displayed an extremely slow growth rate, as shown by mathematical analysis of infections with mixed inocula and segregative plasmid experiments. The slow growth was sufficient to explain recalcitrance to antibiotics treatment. Therefore, slow-growing antibiotic-tolerant bacteria lodged within dendritic cells can explain poor in vivo antibiotic activity and relapse. Administration of LPS or CpG, known elicitors of innate immune defense, reduced the loads of tolerant bacteria. Thus, manipulating innate immunity may augment the in vivo activity of antibiotics.

EFFECT OF REPTATION ON FRACTURE-MECHANICS OF RUBBER NETWORKS

End-linked hydroxyl-terminated polybutadiene containing unattached linear polybutadiene was used to study the effect of reptating species on the fracture mechanics of rubber networks. The concentration of reptating species in the networks ranged from 0 to 100%. The fracture mechanics of the networks was described using the critical strain energy release rate in mode III testing, i.e. the tearing energy. The tearing energy was measured at room temperature using a 'trouser' specimen at a strain rate spanning five logarithmic decades. When the strain rate was as low as 10(-4) s-1, the tearing energy of the networks increased with reduction in reptating species. In this case the reptating species did not contribute to the tearing energy of the networks due to relaxation. Hence, the tearing energy increased with the number of crosslinked chains per unit volume in the networks. At a strain rate ranging from 10(-3) to 10(-1) s-1, the tearing energy of the networks was governed by local viscosity. The tearing energies of the networks containing various amounts of reptating species were superimposed to give a master curve based on the Williams-Landel-Ferry equation.

Biaxial deformation behavior and mechanical properties of a polypropylene/clay nanocomposite

Polymer nanocomposites offer the potential of enhanced properties such as increased modulus and barrier properties to the end user. Much work has been carried out on the effects of extrusion conditions on melt processed nanocomposites but very little research has been conducted on the use of polymer nanocomposites in semi-solid forming processes such as thermoforming and injection blow molding. These processes are used to make much of today’s packaging, and any improvements in performance such as possible lightweighting due to increased modulus would bring signi?cant bene?ts both economically and environmentally. The work described here looks at the biaxial deformation of polypropylene–clay nanocomposites under industrial forming conditions in order to determine if the presence of clay affects processability, structure and mechanical properties of the stretched material. Melt compounded polypropylene/clay composites in sheet form were biaxially stretched at a variety of processing conditions to examine the effect of high temperature, high strain and high strain rate processing on sheet structure
and properties.

A biaxial test rig was used to carry out the testing which imposed conditions on the sheet that are representative of those applied in injection blow molding and thermoforming. Results show that the presence of clay increases the yield stress relative to the un?lled material at typical processing temperatures and that the sensitivity of the yield stress to temperature is greater for the ?lled material. The stretching process is found to have a signi?cant effect on the delamination and alignment of clay particles (as observed by TEM) and on yield stress and elongation at break of the stretched sheet.

Surface expression of O-specific lipopolysaccharide in Escherichia coli requires the function of the TolA protein

We investigated the involvement of Tol proteins in the surface expression of lipopolysaccharide (LPS). tolQ, -R, -A and -B mutants of Escherichia coli K-12, which do not form a complete LPS-containing O antigen, were transformed with the O7+ cosmid pJHCV32. The tolA and tolQ mutants showed reduced O7 LPS expression compared with the respective isogenic parent strains. No changes in O7 LPS expression were found in the other tol mutants. The O7-deficient phenotype in the tolQ and tolA mutants was complemented with a plasmid encoding the tolQRA operon, but not with a similar plasmid containing a frameshift mutation inactivating tolA. Therefore, the reduction in O7 LPS was attributed to the lack of a functional tolA gene, caused either by a direct mutation of this gene or by a polar effect on tolA gene expression exerted by the tolQ mutation. Reduced surface expression of O7 LPS was not caused by changes in lipid A-core structure or downregulation of the O7 LPS promoter. However, an abnormal accumulation of radiolabelled mannose was detected in the plasma membrane. As mannose is a sugar unique to the O7 subunit, this result suggested the presence of accumulated O7 LPS biosynthesis intermediates. Attempts to construct a tolA mutant in the E. coli O7 wild-type strain VW187 were unsuccessful, suggesting that this mutation is lethal. In contrast, a polar tolQ mutation affecting tolA expression in VW187 caused slow growth rate and serum sensitivity in addition to reduced O7 LPS production. VW187 tolQ cells showed an elongated morphology and became permeable to the membrane-impermeable dye propidium iodide. All these phenotypes were corrected upon complementation with cloned tol genes but were not restored by complementation with the tolQRA operon containing the frameshift mutation in tolA. Our results demonstrate that the TolA protein plays a critical role in the surface expression of O antigen subunits by an as yet uncharacterized involvement in the processing of O antigen.

Strain longitudinal global para la detección de estenosis coronaria significativa en pacientes con infarto agudo del miocardio

Introducción: La evaluación de la función miocárdica global y regional juega una papel crítico en el diagnóstico y manejo de los pacientes con enfermedad coronaria con importantes implicaciones pronosticas, las nuevas técnicas ecocardiográficas como la evaluación del STRAIN han sido validadas como una herramienta objetiva, comprehensiva y precisa para evaluar dichos parámetros. Objetivo: Determinar la capacidad del strain global longitudinal para la detección de estenosis coronaria significativa, número de territorios comprometidos y territorio anatómico del vaso culpable; en pacientes sin antecedentes de enfermedad coronaria previa con infarto agudo del miocardio. Diseño: estudio de pruebas diagnósticas retrospectivo en el que se utilizó como gold estándar la angiografía coronaria, se seleccionaron 64 pacientes con ecocardiograma transtorácico previo a la angiografía coronaria. Resultados: Se demostró una exactitud intermedia del strain global longitudinal para detectar estenosis coronaria por análisis de curvas ROC, con un área bajo la curva de 0,78 p= 0,000 (IC 0,6; 1,0), Una sensibilidad de 96.5% (91.7%, 101.3%), especificidad 40.0% (9.6%, 70.4%) y una prevalencia real del enfermedad coronaria de 85.1% (76.5%, 93.6%) Conclusiones: La medición de la función global y regional por medio del strain global longitudinal identifica pacientes con infarto agudo del miocardio que tienen estenosis coronaria significativa, número de territorios afectados, y la distribución anatómica de los posibles vasos culpables, sin embargo hay que tener precaución en su uso que sólo se limite a escenarios en donde pueda ser interpretado adecuadamente. Palabras clave: strain global bidimensional, detección de estenosis coronaria significativa, infarto del miocardio.

Life-cycle simulations of shallow frontal waves and the impact of deformation strain

The life-cycle of shallow frontal waves and the impact of deformation strain on their development is investigated using the idealised version of the Met Office non-hydrostatic Unified Model which includes the same physics and dynamics as the operational forecast model. Frontal wave development occurs in two stages; first, a deformation strain is applied to a front and a positive potential vorticity (PV) strip forms, generated by latent heat release in the frontal updraft; second, as the deformation strain is reduced the PV strip breaks up into individual anomalies. The circulations associated with the PV anomalies cause shallow frontal waves to form. The structure of the simulated frontal waves is consistent with the conceptual model of a frontal cyclone. Deeper frontal waves are simulated if the stability of the atmosphere is reduced. Deformation strain rates of different strengths are applied to the PV strip to determine whether a deformation strain threshold exists above which frontal wave development is suppressed. An objective method of frontal wave activity is defined and frontal wave development was found to be suppressed by deformation strain rates $\ge 0.4\times10^{-5}\mbox{s}^{-1}$. This value compares well with observed deformation strain rate thresholds and the analytical solution for the minimum deformation strain rate needed to suppress barotropic frontal wave development. The deformation strain rate threshold is dependent on the strength of the PV strip with strong PV strips able to overcome stronger deformation strain rates (leading to frontal wave development) than weaker PV strips.

Instability of surface-temperature filaments in strain and shear

The effects of uniform straining and shearing on the stability of a surface quasi-geostrophic temperature filament are investigated. Straining is shown to stabilize perturbations for wide filaments but only for a finite time until the filament thins to a critical width, after which some perturbations can grow. No filament can be stabilized in practice, since there are perturbations that can grow large for any strain rate. The optimally growing perturbations, defined as solutions that reach a certain threshold amplitude first, are found numerically for a wide range of parameter values. The radii of the vortices formed through nonlinear roll-up are found to be proportional to θ/s, where θ is the temperature anomaly of the filament and s the strain rate, and are not dependent on the initial size of the filament. Shearing is shown to reduce the normal-mode growth rates, but it cannot stabilize them completely when there are temperature discontinuities in the basic state; smooth filaments can be stabilized completely by shearing and a simple scaling argument provides the shear rate required. Copyright © 2010 Royal Meteorological Society

Rate-dependent fracture toughness of polycrystalline ice

A series of three-point bend tests using single edge notched testpieces of pure polycrystalline ice have been performed at three different temperatures (–20°C, –30°C and –40°C). The displacement rate was varied from 1 mm/min to 100 mm/min, producing the crack tip strain rates from about 10–3 to 10–1 s–1. The results show that (a) the fracture toughness of pure polycrystalline ice given by the critical stress intensity factor (K IC) is much lower than that measured from the J—integral under identical conditions; (b) from the determination of K IC, the fracture toughness of pure polycrystalline ice decreases with increasing strain rate and there is good power law relationship between them; (c) from the measurement of the J—integral, a different tendency was appeared: when the crack tip strain rate exceeds a critical value of 6 × 10–3 s–1, the fracture toughness is almost constant but when the crack tip strain rate is less than this value, the fracture toughness increases with decreasing crack tip strain rate. Re-examination of the mechanisms of rate-dependent fracture toughness of pure polycrystalline ice shows that the effect of strain rate is related not only to the blunting of crack tips due to plasticity, creep and stress relaxation but also to the nucleation and growth of microcracks in the specimen.

The stability of a two-dimensional vorticity filament under uniform strain

The quantitative effects of uniform strain and background rotation on the stability of a strip of constant vorticity (a simple shear layer) are examined. The thickness of the strip decreases in time under the strain, so it is necessary to formulate the linear stability analysis for a time-dependent basic flow. The results show that even a strain rate γ (scaled with the vorticity of the strip) as small as 0.25 suppresses the conventional Rayleigh shear instability mechanism, in the sense that the r.m.s. wave steepness cannot amplify by more than a certain factor, and must eventually decay. For γ < 0.25 the amplification factor increases as γ decreases; however, it is only 3 when γ e 0.065. Numerical simulations confirm the predictions of linear theory at small steepness and predict a threshold value necessary for the formation of coherent vortices. The results help to explain the impression from numerous simulations of two-dimensional turbulence reported in the literature that filaments of vorticity infrequently roll up into vortices. The stabilization effect may be expected to extend to two- and three-dimensional quasi-geostrophic flows.

Deformation and geochronology of syntectonic granitoids emplaced in the Major Gercino Shear Zone, southeastern South America

The Major Gercino Shear Zone is one of the NE-SW lineaments that separate the Neoproterozoic Dom Feliciano Belt, of Brazil and Uruguay, into two different domains: a northwestern supracrustal domain from a southeastern granitoid domain. The shear zone, striking NE, is composed of protomylonites to ultramylonites with mainly dextral kinematic indicators. In Santa Catarina State, southern Brazil, the shear zone is composed of two mylonite belts. The mylonites have mineral orientations produced under greenschist fades conditions at a high strain rate. Strong flattening and coaxial deformation indicate the transpressive character, while the role of pure shear is emphasized by the orientation of the mylonite belts in relation to the inferred stress field component. The quartz microstructures point out that different dynamic recrystallization regimes and crystal plasticity were the dominant mechanisms of deformation during the mylonitization process. Additionally, the fabrics suggest that the glide systems are activated for deformation conditions compatible with the metamorphism in the middle greenschist facies. Elongated granitoid intrusions belonging to two petrographically, geochemically and isotopically distinct rock associations occur between the two mylonite belts. The structures observed in the granites result from a deformation range from magmatic to solid-state conditions points to a continuum of magma straining during and just after its crystallization. Conventional U-Pb analysis of multi-crystal zircon fractions yielded essentially identical ages of 609 +/- 16 Ma and 614 +/- 2 Ma for the two granitic associations, and constrain the transpressive phase of the shear zone. K-Ar ages of biotites between 585 and 560 Ma record the slow cooling and uplift of the intrusions. Some K-Ar ages of micas in regional mylonites are similar, suggesting that thermo-tectonic activity was intense up to this time, probably related to the agglutination of the granite belt to the supracrustal belt NW of the MGSZ. (C) 2009 International Association for Gondwana Research. Published by Elsevier B.V. All rights reserved.

Microstructure evolution during warm deformation of low carbon steel with dispersed cementite

The microstructure evolution and mechanical behavior during large strain of a 0.16%C-Mn steel has been investigated by warm torsion tests. These experiments were carried out at 685°C at equivalent strain rate of 0.1 s . The initial microstructure composed of a martensite matrix with uniformly dispersed fine cementite particles was attained by quenching and tempering. The microstructure evolution during tempering and straining was performed through interrupted tests. As the material was reheated to testing temperature, well-defined cell structure was created and subgrains within lath martensite were observed by TEM; strong recovery took place, decreasing the dislocation density. After 1 hour at the test temperature and without straining, EBSD technique showed the formation of new grains. The flow stress curves measured had a peculiar shape: rapid work hardening to a hump, followed by an extensive flow-softening region. 65% of the boundaries observed in the sample strained to ε = 1.0 were high angle grain boundaries. After straining to ε = 5.0, average ferrite grain size close to 1.5 μm was found, suggesting that dynamic recrystallization took place. Also, two sets of cementite particles were observed: large particles aligned with straining direction and smaller particles more uniformly dispersed. The fragmentation or grain subdivision that occurred during reheating and tempering time was essential for the formation of ultrafine grained microstructure.

AGE INFLUENCE ON THE HEART RATE BEHAVIOR ON THE REST-EXERCICIO TRANSITION: AN ANALYSIS BY DELTAS AND LINEAR REGRESSION

Background: Changes in heart rate during rest-exercise transition can be characterized by the application of mathematical calculations, such as deltas 0-10 and 0-30 seconds to infer on the parasympathetic nervous system and linear regression and delta applied to data range from 60 to 240 seconds to infer on the sympathetic nervous system. The objective of this study was to test the hypothesis that young and middle-aged subjects have different heart rate responses in exercise of moderate and intense intensity, with different mathematical calculations. Methods: Seven middle-aged men and ten young men apparently healthy were subject to constant load tests (intense and moderate) in cycle ergometer. The heart rate data were submitted to analysis of deltas (0-10, 0-30 and 60-240 seconds) and simple linear regression (60-240 seconds). The parameters obtained from simple linear regression analysis were: intercept and slope angle. We used the Shapiro-Wilk test to check the distribution of data and the "t" test for unpaired comparisons between groups. The level of statistical significance was 5%. Results: The value of the intercept and delta 0-10 seconds was lower in middle age in two loads tested and the inclination angle was lower in moderate exercise in middle age. Conclusion: The young subjects present greater magnitude of vagal withdrawal in the initial stage of the HR response during constant load exercise and higher speed of adjustment of sympathetic response in moderate exercise.

Tectonic geomorphology and active strain of the Northern Apennines mountain front

The Northern Apennines (NA) chain is the expression of the active plate margin between Europe and Adria. Given the low convergence rates and the moderate seismic activity, ambiguities still occur in defining a seismotectonic framework and many different scenarios have been proposed for the mountain front evolution. Differently from older models that indicate the mountain front as an active thrust at the surface, a recently proposed scenario describes the latter as the frontal limb of a long-wavelength fold (> 150 km) formed by a thrust fault tipped around 17 km at depth, and considered as the active subduction boundary. East of Bologna, this frontal limb is remarkably very straight and its surface is riddled with small, but pervasive high- angle normal faults. However, west of Bologna, some recesses are visible along strike of the mountain front: these perturbations seem due to the presence of shorter wavelength (15 to 25 km along strike) structures showing both NE and NW-vergence. The Pleistocene activity of these structures was already suggested, but not quantitative reconstructions are available in literature. This research investigates the tectonic geomorphology of the NA mountain front with the specific aim to quantify active deformations and infer possible deep causes of both short- and long-wavelength structures. This study documents the presence of a network of active extensional faults, in the foothills south and east of Bologna. For these structures, the strain rate has been measured to find a constant throw-to-length relationship and the slip rates have been compared with measured rates of erosion. Fluvial geomorphology and quantitative analysis of the topography document in detail the active tectonics of two growing domal structures (Castelvetro - Vignola foothills and the Ghiardo plateau) embedded in the mountain front west of Bologna. Here, tilting and river incision rates (interpreted as that long-term uplift rates) have been measured respectively at the mountain front and in the Enza and Panaro valleys, using a well defined stratigraphy of Pleistocene to Holocene river terraces and alluvial fan deposits as growth strata, and seismic reflection profiles relationships. The geometry and uplift rates of the anticlines constrain a simple trishear fault propagation folding model that inverts for blind thrust ramp depth, dip, and slip. Topographic swath profiles and the steepness index of river longitudinal profiles that traverse the anti- clines are consistent with stratigraphy, structures, aquifer geometry, and seismic reflection profiles. Available focal mechanisms of earthquakes with magnitude between Mw 4.1 to 5.4, obtained from a dataset of the instrumental seismicity for the last 30 years, evidence a clear vertical separation at around 15 km between shallow extensional and deeper compressional hypocenters along the mountain front and adjacent foothills. In summary, the studied anticlines appear to grow at rates slower than the growing rate of the longer- wavelength structure that defines the mountain front of the NA. The domal structures show evidences of NW-verging deformation and reactivations of older (late Neogene) thrusts. The reconstructed river incision rates together with rates coming from several other rivers along a 250 km wide stretch of the NA mountain front and recently available in the literature, all indicate a general increase from Middle to Late Pleistocene. This suggests focusing of deformation along a deep structure, as confirmed by the deep compressional seismicity. The maximum rate is however not constant along the mountain front, but varies from 0.2 mm/yr in the west to more than 2.2 mm/yr in the eastern sector, suggesting a similar (eastward-increasing) trend of the apenninic subduction.

Dynamic properties of wood using the Split-Hopkinson Pressure Bar

Strain rate significantly affects the strength of a material. The Split-Hopkinson Pressure Bar (SHPB) was initially used to study the effects of high strain rate (~103 1/s) testing of metals. Later modifications to the original technique allowed for the study of brittle materials such as ceramics, concrete, and rock. While material properties of wood for static and creep strain rates are readily available, data on the dynamic properties of wood are sparse. Previous work using the SHPB technique with wood has been limited in scope to variability of only a few conditions and tests of the applicability of the SHPB theory on wood have not been performed. Tests were conducted using a large diameter (3.0 inch (75 mm)) SHPB. The strain rate and total strain applied to a specimen are dependent on the striker bar length and velocity at impact. Pulse shapers are used to further modify the strain rate and change the shape of the strain pulse. A series of tests were used to determine test conditions necessary to produce a strain rate, total strain, and pulse shape appropriate for testing wood specimens. Hard maple, consisting of sugar maple (Acer saccharum) and black maple (Acer nigrum), and eastern white pine (Pinus strobus) specimens were used to represent a dense hardwood and a low-density soft wood. Specimens were machined to diameters of 2.5 and 3.0 inches and an assortment of lengths were tested to determine the appropriate specimen dimensions. Longitudinal specimens of 1.5 inch length and radial and tangential specimens of 0.5 inch length were found to be most applicable to SHPB testing. Stress/strain curves were generated from the SHPB data and validated with 6061-T6 aluminum and wood specimens. Stress was indirectly corroborated with gaged aluminum specimens. Specimen strain was assessed with strain gages, digital image analysis, and measurement of residual strain to confirm the strain calculated from SHPB data. The SHPB was found to be a useful tool in accurately assessing the material properties of wood under high strain rates (70 to 340 1/s) and short load durations (70 to 150 μs to compressive failure).

Metamorphism, Transient Mid-Crustal Rheology, Strain Localization and the Exhumation of High-Grade Metamorphic Rocks

We present a series of three-dimensional numerical models investigating the effects of metamorphic strengthening and weakening on the geodynamic evolution of convergent orogens that are constrained by observations from an exposed mid-crustal section in the New England Appalachians. The natural mid-crustal section records evidence for spatially and temporally variable mid-crustal strength as a function of metamorphic grade during prograde polymetamorphism. Our models address changes in strain rate partitioning and topographic uplift as a function of strengthening/weakening in the middle crust, as well as the resultant changes in deformation kinematics and potential exhumation patterns of high-grade metamorphic rock. Results suggest that strengthening leads to strain rate partitioning around the zone and suppressed topographic uplift rates whereas weakening leads to strain rate partitioning into the zone and enhanced topographic uplift rates. Deformation kinematics recorded in the orogen are also affected by strengthening/weakening, with complete reversals in shear sense occurring as a function of strengthening/weakening without changes in plate boundary kinematics.