bluuebunny/crossref_metadata_2025 huggingface dataset:
Corticosterone alters materno‐fetal glucose partitioning and insulin signalling in pregnant mice
Authors: Vaughan O. R. , Fisher H. M. , Dionelis K. N. , Jefferies E. C. , Higgins J. S. , Musial B. , Sferruzzi‐Perri A. N. , Fowden A. L.
Published: January 2015

Key points

Glucocorticoids regulate fetal and adult glucose metabolism, in part by influencing the actions of insulin. However, their effects on materno‐fetal glucose partitioning remain largely unknown.

In the present study, when pregnant mice were given the natural glucocorticoid, corticosterone, plasma insulin concentrations and liver insulin‐signalling increased but the blood glucose concentration remained normal.

However, in the placenta, glucose transport was reduced in association with the lower activity of some insulin signalling proteins, depending on the day of pregnancy and maternal food intake.

In both liver and placenta, there was increased expression of the Redd1 (Ddit4) gene when the plasma corticosterone concentration was raised.

The results show that maternal glucocorticoids interact with signalling pathways in the placenta to limit materno‐fetal glucose partitioning.

Glucocorticoids affect glucose metabolism in adults and fetuses, although their effects on materno‐fetal glucose partitioning remain unknown. The present study measured maternal hepatic glucose handling and placental glucose transport together with insulin signalling in these tissues in mice drinking corticosterone either from day (D) 11 to D16 or D14 to D19 of pregnancy (term = D21). On the final day of administration, corticosterone‐treated mice were hyperinsulinaemic (P < 0.05) but normoglycaemic compared to untreated controls. In maternal liver, there was no change in glycogen content or glucose 6‐phosphatase activity but increased Slc2a2 glucose transporter expression in corticosterone‐treated mice, on D16 only (P < 0.05). On D19, but not D16, transplacental 3H‐methyl‐d‐glucose clearance was reduced by 33% in corticosterone‐treated dams (P < 0.05). However, when corticosterone‐treated animals were pair‐fed to control intake, aiming to prevent the corticosterone‐induced increase in food consumption, 3H‐methyl‐d‐glucose clearance was similar to the controls. Depending upon gestational age, corticosterone treatment increased phosphorylation of the insulin‐signalling proteins, protein kinase B (Akt) and glycogen synthase‐kinase 3β, in maternal liver (P < 0.05) but not placenta (P > 0.05). Insulin receptor and insulin‐like growth factor type I receptor abundance did not differ with treatment in either tissue. Corticosterone upregulated the stress‐inducible mechanistic target of rapamycin (mTOR) suppressor, Redd1, in liver (D16 and D19) and placenta (D19), in ad libitum fed animals (P < 0.05). Concomitantly, hepatic protein content and placental weight were reduced on D19 (P < 0.05), in association with altered abundance and/or phosphorylation of signalling proteins downstream of mTOR. Taken together, the data indicate that maternal glucocorticoid excess reduces fetal growth partially by altering placental glucose transport and mTOR signalling.
On the Failure Locus of Isotropic Materials in the Stress Triaxiality Space
Authors: Manolopoulos V. M. , Andrianopoulos N. P.
Published: January 2015

The aim of this paper is to contribute to the prediction of the failure of materials (ductile and brittle) with a single criterion (rule) not violating the assumptions of continuum mechanics. In this work, the failure behavior of isotropic materials is connected with the ability of a material to store elastic strain energy from the very start of loading until its fracture. This elastic strain energy is known that is separated in a distortional and a dilatational part. So, when one of these quantities takes a critical value, then the material fails either by slip or by cleavage. The behavior of a material is described with regard to the secant elastic moduli depending on both unit volume expansion Θ and equivalent strain ɛeq. This dependence enlightens, in physical terms, the different reaction of materials in normal and shear stresses. T-criterion is applied for the prediction of failure in a series of experiments that took place to an aluminum alloy (Al-5083) and to PMMA (Plexiglas). A single criterion was used for two totally different materials and the predictions are quite satisfactory. This work is a step toward the direction of using one criterion in order to explain and predict failure in materials independently of the plastic strain that developed before fracture.
Modeling and Characterization of Bio-Inspired Hydro-Acoustic Sensor
Authors: Lee Jin-Hyuk , Reinhall Per G. , Yoon Hwan-Sik
Published: January 2015

A biomimetic miniature underwater acoustic sensor is proposed and analyzed for the measurement of directivity of underwater sound propagation. Unlike a hydrophone array, which detects propagation direction by the arrival time of sound waves, this novel sensor is based on a mechanically coupled mechanism, which amplifies the time delay of the arriving sound wave. In this paper, a mathematical model of the sensor is developed based on the finite element (FE) modeling technique, and it is used to study performance characteristics of the sensor. Effects of the fluid–structure interaction are examined through simulation of the sensor model and the results are compared with those obtained by a full scale FE model developed in a commercial software package.
Review of Progress in the Development of Capacitive Sensors for Blade Tip Clearance Measurement
Authors: Bailleul Gilles D. , Albijat Samim
Published: January 2015

This paper describes how blade tip clearances can be measured with capacitive sensors and the right electronic devices. The design of a capacitive sensor is tightly connected to the engine environment, but also the electronic system which is used to calculate the blade tip clearance. We present two kinds of capacitive sensors : the composite and the integral sensors we developed for use in a compressor. Based on that experience we are developing and testing turbine versions of these designs. In an aero gas turbine the design aim is sensors that shall survive temperatures and vibrations as high as 1,300°C and 150 G’s.
Experimental Studies of Air Extraction for Cooling and/or Gasification in Gas Turbine Applications
Authors: Kapat J. S. , Wang T. , Ryan W. R. , Diakunchak I. S. , Bannister R. L.
Published: January 2015

This paper describes an experimental study on how the flow field inside the dump diffuser of an industrial gas turbine is affected by air extraction through a single port on the shell around the dump diffuser. A sub-scale, 360° model of the diffuser-combustor section of an advanced developmental industrial gas turbine was used in this study. The experiments were performed under cold flow conditions which can be scaled to actual machine operation. Three different conditions were experimentally studied: 0%, 5%, and 20% air extraction. It was found that air extraction, especially extraction at the 20% rate, introduced flow asymmetry inside the dump diffuser and, in some locations, increased the local flow recirculations. This indicated that when air was extracted through a single port on the shell, the performance of the dump diffuser was adversely affected with an approximate 7.6% increase of the total pressure loss, and the air flow into the combustors did not remain uniform. The global flow distribution was shown to be approximately 35% nonuniform diametrically across the dump diffuser. Although a specific geometry was selected, the results provide sufficient generality for improving understanding of the complex flow behavior in the reverse flow diffuser-combustor sections of gas turbines under the influence of various air extractions.
Reduction of Tip Clearance Losses Through 3-D Airfoil Designs
Authors: Staubach J. Brent , Sharma Om P. , Stetson Gary M.
Published: January 2015

Results are presented from a program, conducted to investigate the impact of spanwise stacking of turbine airfoil sections on tip clearance flows. Numerical as well as physical experiments were performed to demonstrate that these airfoils yielded about 40% reduction in tip clearance losses compared to those designed with a conventional approach. Three dimensional, steady Euler and Reynolds Averaged Navier Stokes (RANS) codes were used to execute the numerical experiments. Initial physical experiments were performed in a water tunnel by using linear cascades to validate the design concepts. The verification of the overall design concepts was executed in an uncooled full scale rotating rig.
New Control Systems Facilitate Reconfiguring Aeroderivative Gas Turbines for Cogeneration
Authors: Moore David
Published: January 2015

This paper briefly sets out the requirements for additional steam capacity at Anchor Products dairy plant at Te Awamutu in New Zealand and the reasons for choosing to use a relocated Turbo Power & Marine Twin Pac with a new waste heat recovery boiler together with an existing coal fired boiler to meet this demand.

The paper then discusses the decision to replace the gas turbine and generator controls in their entirety, their integration with the controls for the new and existing boilers, and the architecture adopted for the total system.

The philosophy of the control of the plant is then developed which leads to detailed discussion of the implementation of various modes of control of the plant, including, cogeneration control, co-ordinated control peaking control and compensate control and the methods of changing between the various modes of control.

Finally, the paper includes a section on commissioning the plant.
NOx-Abatement Potential of Lean-Premixed GT-Combustors
Authors: Sattelmayer T. , Polifke W. , Winkler D. , Döbbeling K.
Published: January 2015

The influence of the structure of perfectly premixed flames on NOx-formation is investigated theoretically. Since a network of reaction kinetics modules and model flames is used for this purpose, the results obtained are independent of specific burner geometries. Calculations are presented for a mixture temperature of 630K, an adiabatic flame temperature of 1840K and 1 and 15 bars combustor pressure. In particular, the following effects are studied separately from each other:

- molecular diffusion of temperature and species

- flame strain

- local quench in highly strained flames and subsequent reignition

- turbulent diffusion (no preferential diffusion)

- small scale mixing (stirring) in the flame front

Either no relevant influence or an increase in NOx-production over that of the one-dimensional laminar flame is found. As a consequence, besides the improvement of mixing quality, a future target for the development of low-NOx burners is to avoid excessive turbulent stirring in the flame front. Turbulent flames that exhibit locally and instantaneously near laminar structures (“flamelets”) appear to be optimal.

Using the same methodology, the scope of the investigation is extended to lean-lean staging, since a higher NOx-abatement potential can be expected in principle. As long as the chemical reactions of the second stage take place in the boundary between the fresh mixture of the second stage and the combustion products from upstream, no advantage can be expected from lean-lean staging. Only if the primary burner exhibits much poorer mixing than the second stage can lean-lean staging be beneficial. In contrast, if full mixing between the two stages prior to afterburning can be achieved (lean-mix-lean technique), the combustor outlet temperature can in principle be increased somewhat without NO-penalty. However, the complexity of such a system with a larger flame tube area to be cooled will increase the reaction zone temperatures, so that the full advantage cannot be realised in an engine.

Of greater technical relevance is the potential of a lean-mix-lean combustion system within an improved thermodynamic cycle. A reheat process with sequential combustion is perfectly suited for this purpose, since, firstly, the required low inlet temperature of the second stage is automatically generated after partial expansion in the high pressure turbine, secondly, the efficiency of the thermodynamic cycle has its maximum and, thirdly, high exhaust temperatures are generated, which can drive a powerful Rankine cycle. The higher thermodynamic efficiency of this technique leads to an additional drop in NOx-emissions per power produced.
A Full-Scale Testing of an Annular Turbo-Fan Combustor Including Emission Characteristics
Authors: Seol Woo Seok , Yoon Min Soo , Lee Dae Sung
Published: January 2015

Korea Aerospace Research Institute has performed a joint research with the Central Institute of Aviation Motors of Russia on the design, manufacturing, and testing of an annular combustor for a turbo-fan engine with the thrust of 8,000 lbf. In order to reduce smoke generation, a rather large amount of air is introduced to the primary zone. Presented in this paper is a description of the full-scale annular combustor, the test facility, the test procedure, and the test results. The measured parameters include the pressure loss and its dependence on flow velocity, the combustion efficiency by gas analysis, the exit temperature pattern factor for a wide range of air excess ratio, the lean blow-off limit, and the emission characteristics. The main test conditions are the ‘ground idle’ condition and the ‘altitude cruise’ condition. It was confirmed that the exit temperature profile is closely related to the location of dilution holes on the flame tube. Lean blow-off limit is rather narrow since the combustor was designed to provide a large amount of air to the primary zone with an aim of smoke reduction.
Several Modern Wrought Superalloys for Gas Turbine Applications
Authors: Lai George Y.
Published: January 2015

The present paper discusses several modern wrought superalloys that are being used for various hot gas path components in modern gas turbines. HAYNES® 230™ alloy (Ni-22Cr-14W-2Mo) is used for combustors and transition pieces to replace an old combustor alloy, HASTELLOY® X alloy (Ni-22Cr-19Fe-9Mo), because of higher creep-rupture strength, better oxidation resistance, higher low-cycle fatigue resistance, and other improved properties. The alumina forming HAYNES 214™ alloy (Ni-16Cr-3Fe-4.5Al-Y) replaces HASTELLOY X for honeycomb seals because of its superior oxidation resistance. HAYNES 242™ alloy (Ni-8Cr-25Mo), strengthened by a long-range ordered phase Ni2(Cr,Mo) with low thermal expansion and high strength, is used for turbine casings and seal rings. A less expensive, nitride-strengthened Fe-Ni-Cr alloy, HAYNES HR-120™ alloy, offers an attractive upgrade to many stainless steels and some Ni-base alloys for less demanding, hot section components.
Sensitivity Analysis on Brayton Cycle Gas Turbine Performance
Authors: Negri di Montenegro G. , Peretto A.
Published: January 2015

This paper evaluates the performance of a Brayton cycle gas turbine, in terms of power output and conversion efficiency.

Sensitivity on this performance due to the realistic value of each input variable considered is analyzed.

Sensitivity is evaluated by introducing a parameter, defined as the ratio between the logarithmic differential of the power output or efficiency functions and the logarithmic differential of each variable considered. These analytical functions and their derivatives correspond to a gas turbine model developed by the Authors.

The above-mentioned sensitivity parameter can be also evaluated by means of a numerical procedure utilizing a common gas turbine power plant computational model.

The values calculated with the two procedures turn out to be substantially the same.

Finally, the present analysis permits the determination of the weight of the input variable and of its value on the obtainable numerical performance. Such weights are found to be less important for some variables, while they are of marked significance for others, thus indicating those input parameters requiring a very precise verification of their numerical values.
Control System for a 373 kW, Intercooled, Two-Spool Gas Turbine Engine Powering a Hybrid Electric World Sports Car Class Vehicle
Authors: Shortlidge Charles C.
Published: January 2015

SatCon Technology Corporation has completed design, fabrication, and the first round of test of a 373 kW (500 hp), two-spool, intercooled gas turbine engine with integral induction type alternators. This turbine-alternator is the prime mover for a World Sports Car class hybrid electric vehicle under development by Chrysler Corporation. The complete hybrid electric vehicle propulsion system features the 373 kW (500 hp) turbine-alternator unit, a 373 kW (500 hp) 3.25 kW-h (4.36 hp-h) flywheel, a 559 kW (750 hp) traction motor, and the propulsion system control system. This paper presents and discusses the major attributes of the control system associated with the turbine-alternator unit. Also discussed is the role and operational requirements of the turbine-alternator unit as part of the complete hybrid electric vehicle propulsion system.
Numerical Study of the Tip Clearance Flow Development in a Propulsion Pump Stage
Authors: Lee Yu-Tai , Hah Chunill , Loellbach James
Published: January 2015

This paper summarizes a numerical investigation of the fundamental structure of the rotor tip-clearance vortex and its interaction with a passage trailing-edge vortex in a single-stage stator-rotor pump. The flow field of a highly-loaded rotor measured in a high Reynolds number pump facility (HIREP) is used for comparison. The numerical solution was obtained by solving the three-dimensional Reynolds averaged Navier-Stokes equations. The calculated results are visualized in order to understand the details of the tip-vortex structure. The study shows that the tip geometry should be accurately represented to predict the tip-vortex structure correctly.
Experimental and Numerical Study of Gust and Gust Response in a Rotor/Stator Axial Compressor
Authors: Hsu Shu-Tzung , Wo Andrew M. , Wu Chun-Kai
Published: January 2015

This paper addresses the gust response on the stator of a rotor/stator axial compressor, by decomposing the response into vortical and potential contributions. Experiments were conducted in a large-scale, low-speed compressor rig, with two axial gap cases — 10% and 30% chord — and at two time-mean loadings. To determine the gust response due to potential contribution, a two-step approach was taken. First, a panel code was used to determine the gust in the mid-gap plane for the rotor/stator configuration. Then, this calculated gust served as an inlet boundary of a Reynolds-averaged Navier-Stokes code for the stator cascade configuration. The vortical contributed gust response was found by subtracting the potential contributed response from the measured response. Results show that the vortical contributed response is largest near the instant when the rotor wake impinges at the stator leading edge. The potential contributed response reaches a maximum when the rotor trailing edge is axially upstream of the stator leading edge. The vortical contributed response dominates for all cases studied.
25MW Class Modern Industrial Gas Turbine Suitable for Wide Range of Applications in CoGen/CC Power Plants
Authors: Stankiewicz Chuck , van der Linden Septimus
Published: January 2015

The GT10 25MW class industrial gas turbine from ABB has seen a rapid success in power as well as heat generation for utilities, district heating plants, refineries, communities, universities, paper & food, cement and petrochemical industries.

This broad application attests to the versatility of a modern gas turbine benefiting from advanced technology concepts in combustion, as well as turbine component efficiencies. The paper will review these developments and some interesting applications that could benefit dispersed industrial power plants in the fast developing economies of South East Asia.
Optimal Integration of Humid Air Cycle in Energy Intensive Industries
Authors: Hansen Mogens Weel , Nielsen Jan Sandvig
Published: January 2015

Humid Air Turbine cycle (HAT) is characterised by its high single cycle efficiency. The HAT cycle is typically constrained by a pinch point at low temperature. This indicates that additional heat in the range 100 °C to 200 °C can be utilised with high marginal efficiency. At the same time energy intensive industries (for example refineries, Cement production plants and Steel works) typically have a surplus of heat from around 250 °C to 300 °C and down. This study is aimed at the integration of HAT Cycle into the industrial process plant where the complementary features can be exploited. The present paper has two main objectives. The first objective is to present a general approach for integration analysis. The approach is based on conceptual design using targeting procedures (e.g. Pinch Analysis). The second objective is to find an optimum integration scheme for specific heat sources available from industrial sites. To illustrate both objectives a case study based on real refinery data is discussed.
Modified Rankine HRSG Beats Triple-Pressure System
Authors: Eisenkolb Peter , Pogoreutz Martin , Halozan Hermann
Published: January 2015

Gas-fired combined cycle power plants (CCP) are presently the most efficient systems for producing electricity with fossil fuels. Gas turbines have been and are being improved remarkably during the last years; presently they achieve efficiencies of more than 38% and gas turbine outlet temperatures of up to 610°C.

These high outlet temperatures require modifications and improvements of heat recovery steam generators (HRSG). Presently dual pressure HRSGs are most commonly used in combined cycle power stations. The next step seems to be the triple-pressure HRSG to be able to utilise the high gas turbine outlet temperatures efficiently and to reduce exergy losses caused by the heat transfer between exhaust gas and the steam cycle. However, such triple-pressure systems are complicated considering parallel tube bundles as well as start up operation and load changes.

For that reason an attempt has been made to replace such multiple pressure systems by a modified Rankine cycle with only a single-pressure level. In the case of the same total heat transfer surfaces this innovative single-pressure system achieves approximately the same efficiency as the triple-pressure system. By optimising the heat recovery from the exhaust gas to the steam/water cycle, i.e. minimising exergy losses, the stack temperature is much higher. Increasing the heat transfer surfaces means a decrease of the stack temperature and a further improvement of the overall CCP-efficiency.

Therefore one has to be aware that the proposed system offers advantages not only in the case of a foreseeable increase of gas turbine outlet temperatures but also for presently available gas turbines. Using existing highly efficient gas turbines and subcritical steam conditions, power plants with this proposed Eisenkolb Single Pressure (ESP_CCP) heat recovery steam generator achieve thermal efficiencies of about 58.7% (LHV).
Advanced Combined Cycle Alternatives With the Latest Gas Turbines
Authors: Dechamps P. J.
Published: January 2015

The last decade has seen remarkable improvements in industrial gas turbine size and performances. There is no doubt that the coming years are holding the promises of even more progress in these fields.

As a consequence, the fuel utilization achieved by combined cycle power plants has been steadily increased. This is however also because of the developments in the heat recovery technology.

Advances on the gas turbine side justify the development of new combined cycle schemes, with more advanced heat recovery capabilities. Hence, the system performance is spiralling upwards.

In this paper, we look at some of the heat recovery possibilities with the newly available gas turbine engines, characterized by a high exhaust temperature, a high specific work, and the integration of some gas turbine cooling with the boiler.

The schemes range from classical dual pressure systems, to triple pressure systems with reheat in supercritical steam conditions. For each system, an optimum set of variables (steam pressures, etc) is proposed. The effect of some changes on the steam cycle parameters, like increasing the steam temperatures above 570°C are also considered. Emphasis is also put on the influence of some special features or arrangements of the heat recovery steam generators, not only from a thermodynamic point of view.
Propulsion Integration Aspects in Advanced Military Aircraft
Authors: Herrmann P.
Published: January 2015

Back in history, propulsion integration into an aircraft was mainly related to physical aspects requiring only a low degree of sophistication.

Today propulsion integration has become a major task split between airframe and engine engineers. It now includes performance, functional and physical aspects all needing to be integrated to meet specific requirements.

The aircraft and engine configurations are therefore optionised simultaneously at a very early stage of development. Some of the major interfaces influencing configuration, performance and operability will be discussed, ie. Intake/Engine/Afterbody; Electronic Controls Integration including monitoring; Performance optimisation; Systems; Installation.
Characterization of High-Level Daptomycin Resistance in Viridans Group Streptococci Developed upon
In Vitro
Exposure to Daptomycin
Authors: Akins Ronda L. , Katz Bradley D. , Monahan Catherine , Alexander Dylan
Published: January 2015

Viridans group streptococci (VGS) are part of the normal flora that may cause bacteremia, often leading to endocarditis. We evaluated daptomycin against four clinical strains of VGS (MICs = 1 or 2 μg/ml) using an
in vitro
-simulated endocardial vegetation model, a simulated bacteremia model, and kill curves. Daptomycin exposure was simulated at 6 mg/kg of body weight and 8 mg/kg every 24 h for endocardial and bacteremia models. Total drug concentrations were used for analyses containing protein (albumin and pooled human serum), and free (unbound) drug concentrations (93% protein bound) were used for analyses not containing protein. Daptomycin MICs in the presence of protein were significantly higher than those in the absence of protein. Despite MICs below or at the susceptible breakpoint, all daptomycin regimens demonstrated limited kill in both pharmacodynamic models. A reduction of approximately 1 to 2 log
10
CFU was seen for all isolates and dosages except daptomycin at 6 mg/kg, which achieved a reduction of 2.7 log
10
CFU/g against one strain (
Streptococcus gordonii
1649) in the endocardial model. Activity was similar in both pharmacodynamic models in the presence or absence of protein. Similar activity was noted in the kill curves over all multiples of the MIC. Regrowth by 24 h was seen even at 8× MIC. Postexposure daptomycin MICs for both pharmacodynamic models increased to >256 μg/ml for all isolates by 24 and 72 h. Despite susceptibility to daptomycin by standard MIC methods, these VGS developed high-level daptomycin resistance (HLDR) after a short duration following drug exposure not attributed to modification or inactivation of daptomycin. Further evaluation is warranted to determine the mechanism of resistance and clinical implications.
Staphylococcal Persistence Due to Biofilm Formation in Synovial Fluid Containing Prophylactic Cefazolin
Authors: Dastgheyb Sana S. , Hammoud Sommer , Ketonis Constantinos , Liu Andrew Yongkun , Fitzgerald Keith , Parvizi Javad , Purtill James , Ciccotti Michael , Shapiro Irving M. , Otto Michael , Hickok Noreen J.
Published: January 2015

Antibiotic prophylaxis is standard for patients undergoing surgical procedures, yet despite the wide use of antibiotics, breakthrough infections still occur. In the setting of total joint arthroplasty, such infections can be devastating. Recent findings have shown that synovial fluid causes marked staphylococcal aggregation, which can confer antibiotic insensitivity. We therefore asked in this study whether clinical samples of synovial fluid that contain preoperative prophylactic antibiotics can successfully eradicate a bacterial challenge by pertinent bacterial species. This study demonstrates that preoperative prophylaxis with cefazolin results in high antibiotic levels. Furthermore, we show that even with antibiotic concentrations that far exceed the expected bactericidal levels,
Staphylococcus aureus
bacteria added to the synovial fluid samples are not eradicated and are able to colonize model implant surfaces, i.e., titanium pins. Based on these studies, we suggest that current prophylactic antibiotic choices, despite high penetration into the synovial fluid, may need to be reexamined.
Identification of Metal Dithiocarbamates as a Novel Class of Antileishmanial Agents
Authors: Pal Dhiman Sankar , Mondal Dipon Kumar , Datta Rupak
Published: January 2015

Dithiocarbamates have emerged as potent carbonic anhydrase (CA) inhibitors in recent years. Given that CAs are important players in cellular metabolism, the objective of this work was to exploit the CA-inhibitory property of dithiocarbamates as a chemotherapeutic weapon against the
Leishmania
parasite. We report here strong antileishmanial activity of three hitherto unexplored metal dithiocarbamates, maneb, zineb, and propineb. They inhibited CA activity in
Leishmania major
promastigotes at submicromolar concentrations and resulted in a dose-dependent inhibition of parasite growth. Treatment with maneb, zineb, and propineb caused morphological deformities of the parasite and
Leishmania
cell death with 50% lethal dose (LD
50
) values of 0.56 μM, 0.61 μM, and 0.27 μM, respectively. These compounds were even more effective against parasites growing in acidic medium, in which their LD
50
values were severalfold lower. Intracellular acidosis leading to apoptotic and necrotic death of
L. major
promastigotes was found to be the basis of their leishmanicidal activity. Maneb, zineb, and propineb also efficiently reduced the intracellular parasite burden, suggesting that amastigote forms of the parasite are also susceptible to these metal dithiocarbamates. Interestingly, mammalian cells were unaffected by these compounds even at concentrations which are severalfold higher than their antileishmanial LD
50
s). Our data thus establish maneb, zineb, and propineb as a new class of antileishmanial compounds having broad therapeutic indices.
CD4+T Cell Hyporesponsiveness after Repeated Exposure to Schistosoma mansoni Larvae Is Dependent upon Interleukin-10
Authors: Prendergast Catriona T. , Sanin David E. , Cook Peter C. , Mountford Adrian P.
Published: January 2015

The effect that multiple percutaneous exposures toSchistosomalarvae has on the development of early CD4+lymphocyte reactivity is unclear, yet it is important in the context of humans living in areas where schistosomiasis is endemic. In a murine model of multiple infections, we show that exposure of mice to repeated doses (4×) ofSchistosoma mansonicercariae, compared to a single dose (1×), results in CD4+T cell hyporesponsiveness within the skin-draining lymph nodes (sdLN), manifested as reduced CD4+cell proliferation and cytokine production. FoxP3+CD4+regulatory T cells were present in similar numbers in the sdLN of 4× and 1× mice and thus are unlikely to have a role in effecting hyporesponsiveness. Moreover, anergy of the CD4+cell population from 4× mice was slight, as proliferation was only partly circumvented through thein vitroaddition of exogenous interleukin-2 (IL-2), and thein vivoblockade of the regulatory molecule PD1 had a minimal effect on restoring responsiveness. In contrast, IL-10 was observed to be critical in mediating hyporesponsiveness, as CD4+cells from the sdLN of 4× mice deficient for IL-10 were readily able to proliferate, unlike those from 4× wild-type cohorts. CD4+cells from the sdLN of 4× mice exhibited higher levels of apoptosis and cell death, but in the absence of IL-10, there was significantly less cell death. Combined, our data show that IL-10 is a key factor in the development of CD4+T cell hyporesponsiveness after repeated parasite exposure involving CD4+cell apoptosis.
BaeSR, Involved in Envelope Stress Response, Protects against Lysogenic Conversion by Shiga Toxin 2-Encoding Phages
Authors: Imamovic Lejla , Martínez-Castillo Alexandre , Benavides Carmen , Muniesa Maite
Published: January 2015

Infection and lysogenic conversion with Shiga toxin-encoding bacteriophages (Stx phages) drive the emergence of new Shiga toxin-producing
Escherichia coli
strains. Phage attachment to the bacterial surface is the first stage of phage infection. Envelope perturbation causes activation of envelope stress responses in bacterial cells. Although many external factors are known to activate envelope stress responses, the role of these responses in the phage-bacterium interaction remains unexplored. Here, we investigate the link between three envelope signaling systems in
E. coli
(RcsBC, CpxAR, and BaeSR) and Stx2 phage infection by determining the success of bacterial lysogenic conversion. For this purpose,
E. coli
DH5α wild-type (WT) and mutant strains lacking RcsBC, CpxAR, or BaeSR signaling systems were incubated with a recombinant Stx2 phage (933W). Notably, the number of lysogens obtained with the BaeSR mutant was 5 log
10
units higher than with the WT, and the same differences were observed when using 7 different Stx2 phages. To assess whether the membrane receptor used by Stx phages, BamA, was involved in the differences observed,
bamA
gene expression was monitored by reverse transcription-quantitative PCR (RT-qPCR) in all host strains. A 4-fold-higher
bamA
expression level was observed in the BaeSR mutant than in the WT strain, suggesting that differential expression of the receptor used by Stx phages accounted for the increase in the number of lysogenization events. Establishing the link between the role of stress responses and phage infection has important implications for understanding the factors affecting lysogenic conversion, which drives the emergence of new pathogenic clones.
An Electrostatic Interaction between BlpC and BlpH Dictates Pheromone Specificity in the Control of Bacteriocin Production and Immunity in Streptococcus pneumoniae
Authors: Pinchas Marisa D. , LaCross Nathan C. , Dawid Suzanne
Published: January 2015

Theblplocus ofStreptococcus pneumoniaesecretes and regulates bacteriocins, which mediate both intra- and interspecific competition in the human nasopharynx. There are four major alleles of the geneblpH, which encodes the receptor responsible for activating theblplocus when bound to one of four distinct peptide pheromones (BlpC). The allelic variation ofblpHis presumably explained by a need to restrict cross talk between competing strains. The BlpH protein sequences have polymorphisms distributed throughout the sequence, making identification of the peptide binding site difficult to predict. To identify the pheromone binding sites that dictate pheromone specificity, we have characterized the four major variants and two naturally occurring chimeric versions ofblpHin which recombination events appear to have joined two distinctblpHalleles together. Using these allelic variants, a series of laboratory-generated chimericblpHalleles, and site-directed mutants of both the receptor and peptide, we have demonstrated that BlpC binding to some BlpH types involves an electrostatic interaction between the oppositely charged residues of BlpC and the first transmembrane domain of BlpH. An additional recognition site was identified in the second extracellular loop. We identified naturally occurring BlpH types that have the capacity to respond to more than one BlpC type; however, this change in specificity results in a commensurate drop in overall sensitivity. These natural recombination events were presumably selected for to balance the need to sense bacteriocin-secreting neighbors with the need to turn on bacteriocin production at a low density.

IMPORTANCEBacteria use quorum sensing to optimize gene expression to accommodate for local bacterial density and diffusion rates. To prevent interception of quorum-sensing signals by neighboring strains, the genomes of single species often encode strain-specific signal/receptor pairs. Theblplocus inStreptococcus pneumoniaethat drives bacteriocin secretion is controlled by quorum sensing that involves the interaction of the signal/receptor pair BlpC/BlpH. We show that the pneumococcal population can be divided into several distinct BlpC/BlpH pairs; however, there are examples of naturally occurring chimeric receptors that can bind to more than one BlpC type. The trade-off for this broadened specificity is a loss of overall receptor sensitivity. This suggests that under certain conditions, the advantage of signal interception can trump the requirements for self-induction.
Deletion of a 77-Base-Pair Inverted Repeat Element Alters the Synthesis of Surface Polysaccharides in Porphyromonas gingivalis
Authors: Bainbridge Brian W. , Hirano Takanori , Grieshaber Nicole , Davey Mary E.
Published: January 2015

Bacterial cell surface glycans, such as capsular polysaccharides and lipopolysaccharides (LPS), influence host recognition and are considered key virulence determinants. The periodontal pathogen
Porphyromonas gingivalis
is known to display at least three different types of surface glycans: O-LPS, A-LPS, and K-antigen capsule. We have shown that PG0121 (in strain W83) encodes a DNABII histone-like protein and that this gene is transcriptionally linked to the K-antigen capsule synthesis genes, generating a large ∼19.4-kb transcript (PG0104-PG0121). Furthermore, production of capsule is deficient in a PG0121 mutant strain. In this study, we report on the identification of an antisense RNA (asRNA) molecule located within a 77-bp inverted repeat (77bpIR) element located near the 5′ end of the locus. We show that overexpression of this asRNA decreases the amount of capsule produced, indicating that this asRNA can impact capsule synthesis
in trans
. We also demonstrate that deletion of the 77bpIR element and thereby synthesis of the large 19.4-kb transcript also diminishes, but does not eliminate, capsule synthesis. Surprisingly, LPS structures were also altered by deletion of the 77bpIR element, and reactivity to monoclonal antibodies specific to both O-LPS and A-LPS was eliminated. Additionally, reduced reactivity to these antibodies was also observed in a PG0106 mutant, indicating that this putative glycosyltransferase, which is required for capsule synthesis, is also involved in LPS synthesis in strain W83. We discuss our finding in the context of how DNABII proteins, an antisense RNA molecule, and the 77bpIR element may modulate expression of surface polysaccharides in
P. gingivalis
.

IMPORTANCE
The periodontal pathogen
Porphyromonas gingivalis
displays at least three different types of cell surface glycans: O-LPS, A-LPS, and K-antigen capsule. We have shown using Northern analysis that the K-antigen capsule locus encodes a large transcript (∼19.4 kb), encompassing a 77-bp inverted repeat (77bpIR) element near the 5′ end. Here, we report on the identification of an antisense RNA (asRNA) encoded within the 77bpIR. We show that overexpression of this asRNA or deletion of the element decreases the amount of capsule. LPS structures were also altered by deletion of the 77bpIR, and reactivity to monoclonal antibodies to both O-LPS and A-LPS was eliminated. Our data indicate that the 77bpIR element is involved in modulating both LPS and capsule synthesis in
P. gingivalis
.
High-Throughput Metagenomic Technologies for Complex Microbial Community Analysis: Open and Closed Formats
Authors: Zhou Jizhong , He Zhili , Yang Yunfeng , Deng Ye , Tringe Susannah G. , Alvarez-Cohen Lisa
Published: January 2015

Understanding the structure, functions, activities and dynamics of microbial communities in natural environments is one of the grand challenges of 21st century science. To address this challenge, over the past decade, numerous technologies have been developed for interrogating microbial communities, of which some are amenable to exploratory work (e.g., high-throughput sequencing and phenotypic screening) and others depend on reference genes or genomes (e.g., phylogenetic and functional gene arrays). Here, we provide a critical review and synthesis of the most commonly applied “open-format” and “closed-format” detection technologies. We discuss their characteristics, advantages, and disadvantages within the context of environmental applications and focus on analysis of complex microbial systems, such as those in soils, in which diversity is high and reference genomes are few. In addition, we discuss crucial issues and considerations associated with applying complementary high-throughput molecular technologies to address important ecological questions.
Primary/local hepatic tuberculosis without dissemination
Authors: Meena Manoj , Dixit Ramakant , Meena Lalit Prashant , Samaria Jai Kumar
Published: January 2015

We present a rare case of primary hepatic tuberculosis in a 50-year-old man who presented with pain at the right hypochondrium. The diagnosis was established by fine-needle aspiration cytology (FNAC) of the primary hepatic lesions in both lobes of the liver, which was further supported by histopathological examination and tissue PCR forMycobacterium tuberculosisin the FNAC specimens.
Intense pruritus in Epstein-Barr virus (EBV) hepatitis treated with naloxone drip
Authors: Agrawal Satyanisth , O'Connor Ryan , Aoun Elie , Babich Michael
Published: January 2015

Pruritus is a manifestation of chronic liver disease. Epstein-Barr virus (EBV) infection often presents as infectious mononucleosis and mild hepatitis. Severe pruritus in the setting of infectious mononucleosis and persistent marked hyperbilirubinaemia is exceedingly uncommon. To the best of our knowledge, we present the first case of a patient with EBV hepatitis and severe pruritus that was successfully treated with anultra-low doseof intravenous naltraxone.
Cardiac CT for intraseptal pseudoaneurysm: impending double rupture of ventricular septum and left ventricular free wall
Authors: Yamada Hiroshi , Sakurai Asako , Higurashi Aya , Takeda Kohji
Published: January 2015

A 71-year-old woman presented at our hospital with chest discomfort. Cardiac CT showed an impending double rupture; an intraseptal pseudoaneurysm had ruptured into the right ventricle, while the left ventricular free wall remained intact at this stage. After admission, the patient fell into cardiogenic shock. Emergency surgery was performed. The intraoperative findings included a double rupture of the ventricular septum and the left ventricular free wall. Double rupture is a rare but fatal complication of myocardial infarction. Early diagnosis is essential. Recently, cardiac CT has emerged as a valuable tool for patients with possible ischaemic disease. In this case, enhanced cardiac CT showed an impending double rupture of junctional-type. The static and dynamic images of intraseptal pseudoaneurysm by two-dimensional (2-D) CT, 3-D CT and 4-D CT presented here provide insights into the mechanisms behind, and the pathophysiology of, double ruptures. They also demonstrate the significance of cardiac CT for evaluating ischaemic heart disease.
Psychogenic polydipsia, hyponatremia and osmotic myelinolysis
Authors: Penders Thomas M , Stanciu Cornel N , Ganpat Peter , Ingersoll Jennifer A
Published: January 2015

Objective

Description of a case of osmotic myelinolysis associated with hyponatremia produced as a consequence of compulsive water drinking.

Method

Case report and review of relevant literature.

Results

Compulsive water drinking or psychogenic polydipsia is a common cause of hyponatremia among individuals with chronic mental illness. Central pontine myelinolysis and extrapontine myelinolysis are serious neurological complications resulting from rapid correction of serum sodium and associated changes in serum osmolality. A case of extrapontine myelinolysis confirmed by characteristic MRI findings following an episode of extreme hyponatremia caused by psychogenic polydipsia is described involving a patient with an adult lifelong history of chronic mental illness diagnosed as schizoaffective disorder. With supportive care the related cognitive deficits and balance difficulties resolved completely.

Conclusions

Clinicians should be aware of the potential for hyponatremia resulting from compulsive water drinking to cause myelinolysis with delayed development of cognitive and gait symptoms that responds to supportive care if identified early.
Crooked fingers and sparse hair: an interesting case of trichorhinophalangeal syndrome type 1
Authors: Narayanan Ramakrishna , Chennareddy Srinivasa
Published: January 2015

Trichorhinophalangeal syndrome type 1 is a rare skeletal dysplasia of autosomal-dominant inheritance due to defects in the TRPS-1 gene. The syndrome is characterised by sparse slow-growing hair, a bulbous pear-shaped nose, cone-shaped epiphyses and deformities of the interphalangeal joints resembling those in rheumatoid arthritis. We present a case of trichorhinophalangeal syndrome in a 23-year-old man who presented with symmetrical painless progressive deformity of the fingers in both hands.
Is time of the essence? Delayed diagnosis of Ewing's sarcoma
Authors: Edwards Madeline , Halton Jacqueline , Ramphal Raveena , Johnston Donna
Published: January 2015

Rarely in modern medicine are we able to observe the natural history of a patient with a sarcoma. This unusual case provides that opportunity. A CT scan was performed on the leg of a 15-year-old boy with a tender soft tissue mass on the lateral aspect of his left calf. Despite showing a lesion consistent with a sarcoma, neither the patient nor his family was informed. Almost a year and a half later, the patient returned and was diagnosed with Ewing's sarcoma. A staging work up showed no metastatic disease. After undergoing chemotherapy and a complete surgical resection of the tumour, the patient remains disease-free 10 years later, indicating that the biology of Ewing's sarcoma may be more important than time to diagnosis in determining outcome.
Relative growth rates and secondary compounds in epiphytic lichens along canopy height gradients in forest gaps and meadows in inland British Columbia
Authors: Bidussi Massimo , Gauslaa Yngvar
Published: January 2015

We explore relative growth rates (RGRs) and carbon-based secondary compounds (CBSCs) in epiphytic lichens along height-above-the-ground gradients. The chlorolichen (Letharia vulpina (L.) Hue), the cephalolichen (Lobaria pulmonaria (L.) Hoffm.), and the cyanolichens (Lobaria hallii (Tuck.) Zahlbr., Nephroma helveticum Ach.) were attached to branches at 0.5–3.0 m heights of young spruce trees transplanted for 1 year in forest gaps and in old meadows of an inland valley in British Columbia. Cephalolichen and cyanolichen RGRs were highest in forest gaps, whereas the chlorolichen grew faster in meadows with twice as much light as forest gaps. Transplantation height did not influence lichen temperature or RGRs, despite height-dependent light increases. CBSCs were highest in the chlorolichen (13%), followed by the cephalolichen (5%) and the cyanolichens (1% and 0%). CBSC concentrations increased with thallus size, and were significantly higher in forest gaps mainly for L. pulmonaria. Only one minor CBSC in each species varied with height. The slow growth of cephalolichen and cyanolichens in meadows is consistent with these lichens’ preferences for forested habitats. Cold air ponding from snow-capped mountains was probably strong enough to form enough nocturnal dew to support reasonable lichen growth at all heights. The high species-specific and the low habitat-specific CBSC variations are consistent with constitutive CBSC defense levels in studied lichens.