bluuebunny/crossref_metadata_2025 huggingface dataset:
The hotter the weather, the greater the infestation of Portulaca oleracea: opportunistic life‐history traits in a serious weed
Authors: Feng L , Chen G‐Q , Tian X‐S , Yang H‐M , Yue M‐F , Yang C‐H
Published: April 2015

Portulaca oleracea, an r‐strategist, is one of the world's most troublesome weeds. During hot seasons, P. oleracea frequently becomes monodominant in choy sum (Brassica parachinensis) fields in Guangzhou city, southern China. Here, we studied the seasonal dynamics of P. oleracea's germinable soil seedbank, population density and above‐ground biomass in choy sum fields that had been cultivated continuously for several years. Using P. oleracea seeds collected from these fields, we tested seed dormancy, survival and germination, seedling growth and generation time. Portulaca oleracea occurred at high levels during the hot season, but its occurrence was low, and the germinable soil seedbank was much greater during the cold season. The weed's opportunistic characteristics allowed it to avoid freezing and to proliferate during optimal conditions. Portulaca oleracea's generation time was very flexible, as short as 31 days during the hot season, but longer than 100 days during the colder season. Seed dormancy tended to be shorter when the seeds were stored at a higher temperature. At a temperature of 35°C, both seed germination and seedling growth showed advantages over those of choy sum. Storage for one year at a temperature of −20°C or burial in a paddy field did not significantly reduce P. oleracea seed germination. Nevertheless, seed storage at a temperature of 15°C and soil coverage of 0.5 cm on top of the seeds significantly constrained seed germination. ‘Stale seedbed’ and/or coverage of the surface with soil are recommended during the hot season. However, rotation of rice and upland crops is not an efficient method for managing Portulaca oleracea infestation.
Carotid body overactivity induces respiratory neurone channelopathy contributing to neurogenic hypertension
Authors: Moraes Davi J. A. , Machado Benedito H. , Paton Julian F. R.
Published: April 2015

Why sympathetic activity rises in neurogenic hypertension remains unknown. It has been postulated that changes in the electrical excitability of medullary pre‐sympathetic neurones are the main causal mechanism for the development of sympathetic overactivity in experimental hypertension. Here we review recent data suggesting that enhanced sympathetic activity in neurogenic hypertension is, at least in part, dependent on alterations in the electrical excitability of medullary respiratory neurones and their central modulation of sympatho‐excitatory networks. We also present results showing a critical role for carotid body tonicity in the aetiology of enhanced central respiratory modulation of sympathetic activity in neurogenic hypertension. We propose a novel hypothesis of respiratory neurone channelopathy induced by carotid body overactivity in neurogenic hypertension that may contribute to sympathetic excess. Moreover, our data support the notion of targeting the carotid body as a potential novel therapeutic approach for reducing sympathetic vasomotor tone in neurogenic hypertension.
Investigation of Forced Response Sensitivity of Low Pressure Compressor With Respect to Variation in Tip Clearance Size
Authors: Mesbah Majid , Thomas Jean-François , Thirifay François , Naert A. , Hiernaux S.
Published: April 2015

This study aims to numerically investigate the sensitivity of the forced response with respect to the variation of the tip clearance setting of a low pressure compressor BluM™(monoblock bladed drum) when it is subjected to low engine order excitations. Two different types of blades are employed in the upstream row in order to generate the low engine order excitations. The forced response as well as the aerodynamic damping is numerically estimated using the TWIN approach. The experiments are conducted to measure the forced response for the nominal tip gap to validate the numerical results. Further, simulations are performed for a range of tip clearances. The variation of the steady load distributions due to the changes of the tip clearance are analyzed and presented. The aerodynamic damping and the forced response are calculated and compared for different tip clearances. It is observed that aerodynamic damping increases significantly with tip gap, whereas the excitation forces are reduced. As consequence of these two evolutions, the forced response decreases drastically for larger tip clearance.
The effectiveness of terminal feedback delivery to improve the clinical skills of pre-registration health professional students in simulated environments: A systematic review
Authors: Stanhope Jessica , Gill Robyn
Published: April 2015

Aim: To determine whether terminal feedback is effective in improving the practical, clinical skills of pre-registration health professional students in simulated environments, and how it is best delivered. Methods: Eight databases were searched systematically to identify studies addressing our aim. Eligible studies were published 2004–2014, in English language, within peer- reviewed journals. Study designs were determined and assigned to the National Health and Medical Research Council hierarchy of evidence, with the PEDro scale used to appraise ≥Level III_1 studies. Data regarding the country, participant characteristics, sample size, task critiqued, prior experience with the task, feedback delivered, follow-up time, outcome measures, methods of statistical analysis and the results were extracted and reported descriptively. Results: Eight studies (Levels II–V) were included. Most investigated medical students performing laparoscopic and/or knot tying tasks. PEDro scale scores ranged from 18–54%. Results were mixed when comparing terminal verification feedback and no feedback (n=3), and comparing different types of feedback (n=3). Overall, it would appear that, in terms of terminal feedback, elaborative feedback is more effective in improving the practical, clinical skills of pre-registration health professional students (n=4). Discussion: Whilst there is some indication that elaborative feedback may be more effective than no feedback, the small number of studies and poor methodological quality of the included studies precludes any strong conclusions from being drawn. There are a number of gaps in the current literature, particularly investigating non-medical professions, that should be addressed in future research. Furthermore, larger-scale, well-designed studies in the area are required to guide clinical teaching.
Motion mitigation for lung cancer patients treated with active scanning proton therapy
Authors: Grassberger Clemens , Dowdell Stephen , Sharp Greg , Paganetti Harald
Published: April 2015

Purpose:

Motion interplay can affect the tumor dose in scanned proton beam therapy. This study assesses the ability of rescanning and gating to mitigate interplay effects during lung treatments.

Methods:

The treatments of five lung cancer patients [48 Gy(RBE)/4fx] with varying tumor size (21.1–82.3 cm3) and motion amplitude (2.9–30.6 mm) were simulated employing 4D Monte Carlo. The authors investigated two spot sizes (σ ∼ 12 and ∼3 mm), three rescanning techniques (layered, volumetric, breath‐sampled volumetric) and respiratory gating with a 30% duty cycle.

Results:

For 4/5 patients, layered rescanning 6/2 times (for the small/large spot size) maintains equivalent uniform dose within the target >98% for a single fraction. Breath sampling the timing of rescanning is ∼2 times more effective than the same number of continuous rescans. Volumetric rescanning is sensitive to synchronization effects, which was observed in 3/5 patients, though not for layered rescanning. For the large spot size, rescanning compared favorably with gating in terms of time requirements, i.e., 2x‐rescanning is on average a factor ∼2.6 faster than gating for this scenario. For the small spot size however, 6x‐rescanning takes on average 65% longer compared to gating. Rescanning has no effect on normal lung V20 and mean lung dose (MLD), though it reduces the maximum lung dose by on average 6.9 ± 2.4/16.7 ± 12.2 Gy(RBE) for the large and small spot sizes, respectively. Gating leads to a similar reduction in maximum dose and additionally reduces V20 and MLD. Breath‐sampled rescanning is most successful in reducing the maximum dose to the normal lung.

Conclusions:

Both rescanning (2–6 times, depending on the beam size) as well as gating was able to mitigate interplay effects in the target for 4/5 patients studied. Layered rescanning is superior to volumetric rescanning, as the latter suffers from synchronization effects in 3/5 patients studied. Gating minimizes the irradiated volume of normal lung more efficiently, while breath‐sampled rescanning is superior in reducing maximum doses to organs at risk.
Biomechanical modeling constrained surface‐based image registration for prostate MR guided TRUS biopsy
Authors: van de Ven Wendy J. M. , Hu Yipeng , Barentsz Jelle O. , Karssemeijer Nico , Barratt Dean , Huisman Henkjan J.
Published: April 2015

Purpose:

Adding magnetic resonance (MR)‐derived information to standard transrectal ultrasound (TRUS) images for guiding prostate biopsy is of substantial clinical interest. A tumor visible on MR images can be projected on ultrasound (US) by using MR‐US registration. A common approach is to use surface‐based registration. The authors hypothesize that biomechanical modeling will better control deformation inside the prostate than a regular nonrigid surface‐based registration method. The authors developed a novel method by extending a nonrigid surface‐based registration algorithm with biomechanical finite element (FE) modeling to better predict internal deformations of the prostate.

Methods:

Data were collected from ten patients and the MR and TRUS images were rigidly registered to anatomically align prostate orientations. The prostate was manually segmented in both images and corresponding surface meshes were generated. Next, a tetrahedral volume mesh was generated from the MR image. Prostate deformations due to the TRUS probe were simulated using the surface displacements as the boundary condition. A three‐dimensional thin‐plate spline deformation field was calculated by registering the mesh vertices. The target registration errors (TREs) of 35 reference landmarks determined by surface and volume mesh registrations were compared.

Results:

The median TRE of a surface‐based registration with biomechanical regularization was 2.76 (0.81–7.96) mm. This was significantly different than the median TRE of 3.47 (1.05–7.80) mm for regular surface‐based registration without biomechanical regularization.

Conclusions:

Biomechanical FE modeling has the potential to improve the accuracy of multimodal prostate registration when comparing it to a regular nonrigid surface‐based registration algorithm and can help to improve the effectiveness of MR guided TRUS biopsy procedures.
Dynamic contrast‐enhanced MR microscopy identifies regions of therapeutic response in a preclinical model of colorectal adenocarcinoma
Authors: Subashi Ergys , Qi Yi , Johnson G. Allan
Published: April 2015

Purpose:

A typical dynamic contrast‐enhanced (DCE)‐MRI study often compares the derived pharmacokinetic parameters on manually selected tumor regions or over the entire tumor volume. These measurements include domains where the interpretation of the biomarkers may be unclear (such as in necrotic areas). Here, the authors describe a technique for increasing the sensitivity and specificity of DCE‐MRI by identifying tumor regions with a variable response to therapy.

Methods:

Two cohorts (n = 8/group) of nu/nu mice with LS‐174T implanted in the mammary fat pad were imaged at five time points over four weeks. The treatment/control group received bevacizumab/saline at a dose of 5 mg/kg or 5 ml/kg twice weekly; imaging experiments were performed weekly. MR images were acquired at an isotropic resolution of 156 μm3(2.4 nl) and with a sampling rate of 9.9 s. The histogram of the time‐to‐peak (TTP) was used to identify two (fast‐ and slow‐enhancing) regions based on a threshold of TTP = 1000 s. The regions were correlated with histology, and the effect of therapy was locally examined.

Results:

Tumors in the treatment group had a significantly longer doubling time. The regions defined by thresholding the TTP histogram identified two distinct domains correlating significantly with tumor permeability and microvessel density. In the fast‐enhancing region, the mean permeability constant (Ktrans) was significantly lower in the treatment group at day 9; in the slow‐enhancing region, Ktrans was not different between the control and treatment groups. At day 9, the relative volume of the fast‐enhancing region was significantly lower in the treatment group, while that of the slow‐enhancing region was significantly higher.

Conclusions:

Two regions with distinct kinetic parameters were identified based on the histogram of TTP. The effect of bevacizumab, as measured by a decrease in Ktrans, was confined to one of these regions. High spatiotemporal resolution MR studies may contribute unique insights into the response of the tumor microenvironment to therapy.
A basic Michelson laser interferometer for the undergraduate teaching laboratory demonstrating picometer sensitivity
Authors: Libbrecht Kenneth G. , Black Eric D.
Published: April 2015

We describe a basic Michelson laser interferometer experiment for the undergraduate teaching laboratory that achieves picometer sensitivity in a hands-on, table-top instrument. In addition to providing an introduction to interferometer physics and optical hardware, the experiment also focuses on precision measurement techniques including servo control, signal modulation, phase-sensitive detection, and different types of signal averaging. Students examine these techniques in a series of steps that take them from micron-scale sensitivity using direct fringe counting to picometer sensitivity using a modulated signal and phase-sensitive signal averaging. After students assemble, align, and characterize the interferometer, they then use it to measure nanoscale motions of a simple harmonic oscillator system as a substantive example of how laser interferometry can be used as an effective tool in experimental science.
What my dogs forced me to learn about thermal energy transfer
Authors: Bohren Craig F.
Published: April 2015

Some objects feel colder to the touch than others at the same (room) temperature. But explaining why by linear, single-factor reasoning is inadequate because the time-dependent thermal energy transfer at solid interfaces initially at different temperatures is determined by the thermal inertia kρc, a function of three thermophysical properties: thermal conductivity k, density ρ, and specific heat capacity per unit mass c. In time-dependent problems 1/kρc plays the role of a resistance. As an example, although the thermal conductivity of aluminum is 16 times that of stainless steel, this does not translate into a 16-fold difference in interfacial thermal energy flux densities. Nor does it result in a markedly greater perceived coldness of aluminum; the difference is barely perceptible. Similarly, despite the 600-fold difference in the thermal conductivity of iron relative to that of wood, the ratio of thermal energy flux densities is only about 4.6.
Tethered particle motion with single DNA molecules
Authors: Song Dan , Mousley Briana , Gambino Stefano , Helou Elsie , Loparo Joseph , Price Allen C.
Published: April 2015

A simple method for tethering microbeads using single molecules of DNA is explained. We describe how to use video microscopy and particle tracking to measure the trajectories of the microbeads' motion. The trajectories are analyzed and compared to different models of tethered particle motion. In addition, the data are used to measure the elasticity of the DNA (its spring constant), and the DNA persistence length.
The Sagnac effect and pure geometry
Authors: Tartaglia Angelo , Ruggiero Matteo Luca
Published: April 2015

The Sagnac effect is usually deemed to be a special-relativistic effect produced in an interferometer when the device is rotating. Two light beams traveling around the interferometer in opposite directions require different times of flight to complete their closed path, giving rise to a phase shift proportional to the angular velocity of the apparatus. Here, we show that the same result can be obtained in the absence of rotation, when there is relative motion (be it inertial or not) between the source/receiver of light and the interferometer. Our argument will use both a simple algebraic analysis and a plain geometric approach in flat spacetime. We present an explicit example to illustrate our point and briefly discuss other apparently correct interpretations of the Sagnac effect, including an analogy to the Aharonov-Bohm effect. Finally, we sketch a possible application of the non-rotational Sagnac effect.
Experimentally determining the locations of two astigmatic images for an underwater light source
Authors: Yang Pao-Keng , Liu Jian-You , Ying Shang-Ping
Published: April 2015

Images formed by an underwater object from light rays refracted in the sagittal and tangential planes are located at different positions for an oblique viewing position. The overlapping of these two images from the observer's perspective will thus prevent the image-splitting astigmatism from being directly observable. In this work, we present a heuristic method to experimentally visualize the astigmatism. A point light source is used as an underwater object and the emerging wave front is recorded using a Shack-Hartmann wave-front sensor. The wave front is found to deform from a circular paraboloid to an elliptic paraboloid as the viewing position changes from normal to oblique. Using geometric optics, we derive an analytical expression for the image position as a function of the rotating angle of an arm used to carry the wave-front sensor in our experimental setup. The measured results are seen to be in good agreement with the theoretical predictions.
An undergraduate experiment of wave motion using a coupled-pendulum chain
Authors: Liang Changlin , Ke Weiping , Fu Minxue , Wang Changjiang , Chen Xi
Published: April 2015

We report on the design and construction of a series of coupled pendula to demonstrate various aspects of wave motion, such as normal modes, standing waves, a dispersion relation, and evanescence waves. The experiment can help undergraduate students obtain a better understanding of the properties of wave motion.
Analyzing the many skills involved in solving complex physics problems
Authors: Adams Wendy K. , Wieman Carl E.
Published: April 2015

We have empirically identified over 40 distinct sub-skills that affect a person's ability to solve complex problems in many different contexts. The identification of so many sub-skills explains why it has been so difficult to teach or assess problem solving as a single skill. The existence of these sub-skills is supported by several studies comparing a wide range of individuals' strengths and weaknesses in these sub-skills, their “problem solving fingerprint,” while solving different types of problems including a classical mechanics problem, quantum mechanics problems, and a complex trip-planning problem with no physics. We see clear differences in the problem solving fingerprint of physics and engineering majors compared to the elementary education majors that we tested. The implications of these findings for guiding the teaching and assessing of problem solving in physics instruction are discussed.
Computational model of a vector-mediated epidemic
Authors: Dickman Adriana Gomes , Dickman Ronald
Published: April 2015

We discuss a lattice model of vector-mediated transmission of a disease to illustrate how simulations can be applied in epidemiology. The population consists of two species, human hosts and vectors, which contract the disease from one another. Hosts are sedentary, while vectors (mosquitoes) diffuse in space. Examples of such diseases are malaria, dengue fever, and Pierce's disease in vineyards. The model exhibits a phase transition between an absorbing (infection free) phase and an active one as parameters such as infection rates and vector density are varied.
Layering, melting, and recrystallization of a close-packed micellar crystal under steady and large-amplitude oscillatory shear flows
Authors: López-Barrón Carlos R. , Wagner Norman J. , Porcar Lionel
Published: April 2015

The rheology and three-dimensional microstructure of a concentrated viscoelastic solution of the triblock copolymer poly(ethylene oxide)106-poly(propylene oxide)68-poly(ethylene oxide)106 (Pluronic F127) in the protic ionic liquid ethylammonium nitrate are measured by small angle neutron scattering (SANS) under flow in three orthogonal planes. This solution's shear-thinning viscosity is due to the formation of two-dimensional hexagonal close-packed (HCP) sliding layer structure. Shear-melting of the crystalline structure is observed without disruption of the self-assembled micelles, resulting in a change in flow properties. Spatially resolved measurements in the 1–2 plane reveal that both shear-melting and sliding are not uniform across the Couette gap. Melting and recrystallization of the HCP layers occur cyclically during a single large amplitude oscillatory shear (LAOS) cycle, in agreement with the “stick-slip” flow mechanism proposed by Hamley et al. [Phys. Rev. E 58, 7620–7628 (1998)]. Analysis of 3D “structural” Lissajous curves show that the cyclic melting and sliding are direct functions of the strain rate amplitude and show perfect correlation with the cyclic stress response during LAOS. Both viscosity and structural order obey the Delaware–Rutgers rule. Combining rheology with in situ spatiotemporally resolved SANS is demonstrated to elucidate the structural origins of the nonlinear rheology of complex fluids.
α-Synuclein attracts microglia
Authors: Ferrarelli Leslie K.
Published: April 2015

Blocking an integrin on microglia may prevent the pathological effects of α-synuclein aggregates in Parkinson’s disease.
Sending survival signals
Authors: Gough Nancy R.
Published: April 2015

Cancer cells responding to treatment deliver prosurvival signals to their drug-resistant cousins.
Microbes message gut secretory cells
Authors: Gough Nancy R.
Published: April 2015

Spore-forming gut microbes produce metabolites that stimulate serotonin production by enterochromaffin cells.
Treatment with the Smallpox Antiviral Tecovirimat (ST-246) Alone or in Combination with ACAM2000 Vaccination Is Effective as a Postsymptomatic Therapy for Monkeypox Virus Infection
Authors: Berhanu Aklile , Prigge Jonathan T. , Silvera Peter M. , Honeychurch Kady M. , Hruby Dennis E. , Grosenbach Douglas W.
Published: April 2015

The therapeutic efficacies of smallpox vaccine ACAM2000 and antiviral tecovirimat given alone or in combination starting on day 3 postinfection were compared in a cynomolgus macaque model of lethal monkeypox virus infection. Postexposure administration of ACAM2000 alone did not provide any protection against severe monkeypox disease or mortality. In contrast, postexposure treatment with tecovirimat alone or in combination with ACAM2000 provided full protection. Additionally, tecovirimat treatment delayed until day 4, 5, or 6 postinfection was 83% (days 4 and 5) or 50% (day 6) effective.
Antifungal Susceptibility Profiles of Bloodstream Yeast Isolates by Sensititre YeastOne over Nine Years at a Large Italian Teaching Hospital
Authors: Posteraro Brunella , Spanu Teresa , Fiori Barbara , De Maio Flavio , De Carolis Elena , Giaquinto Alessia , Prete Valentina , De Angelis Giulia , Torelli Riccardo , D'Inzeo Tiziana , Vella Antonietta , De Luca Alessio , Tumbarello Mario , Ricciardi Walter , Sanguinetti Maurizio
Published: April 2015

Sensititre YeastOne (SYO) is an affordable alternative to the Clinical and Laboratory Standards Institute (CLSI) reference method for antifungal susceptibility testing. In this study, the MICs of yeast isolates from 1,214 bloodstream infection episodes, generated by SYO during hospital laboratory activity (January 2005 to December 2013), were reanalyzed using current CLSI clinical breakpoints/epidemiological cutoff values to assign susceptibility (or the wild-type [WT] phenotype) to systemic antifungal agents. Excluding
Candida albicans
(57.4% of all isolates [
n
= 1,250]), the most predominant species were
Candida parapsilosis
complex (20.9%),
Candida tropicalis
(8.2%),
Candida glabrata
(6.4%),
Candida guilliermondii
(1.6%), and
Candida krusei
(1.3%). Among the non-
Candida
species (1.9%), 7 were
Cryptococcus neoformans
and 17 were other species, mainly
Rhodotorula
species. Over 97% of
Candida
isolates were susceptible (WT phenotype) to amphotericin B and flucytosine. Rates of susceptibility (WT phenotype) to fluconazole, itraconazole, and voriconazole were 98.7% in
C. albicans
, 92.3% in the
C. parapsilosis
complex, 96.1% in
C. tropicalis
, 92.5% in
C. glabrata
, 100% in
C. guilliermondii
, and 100% (excluding fluconazole) in
C. krusei
. The fluconazole-resistant isolates consisted of 6
C. parapsilosis
complex isolates, 3
C. glabrata
isolates, 2
C. albicans
isolates, 2
C. tropicalis
isolates, and 1
Candida
lusitaniae
isolate. Of the non-
Candida
isolates, 2
C. neoformans
isolates had the non-WT phenotype for susceptibility to fluconazole, whereas
Rhodotorula
isolates had elevated azole MICs. Overall, 99.7% to 99.8% of
Candida
isolates were susceptible (WT phenotype) to echinocandins, but 3 isolates were nonsusceptible (either intermediate or resistant) to caspofungin (
C. albicans
,
C. guilliermondii
, and
C. krusei
), anidulafungin (
C. albicans
and
C. guilliermondii
), and micafungin (
C. albicans
). However, when the intrinsically resistant non-
Candida
isolates were included, the rate of echinocandin nonsusceptibility reached 1.8%. In summary, the SYO method proved to be able to detect yeast species showing antifungal resistance or reduced susceptibility.
Histone Deacetylase Inhibitor Romidepsin InhibitsDe NovoHIV-1 Infections
Authors: Jønsson Kasper L. , Tolstrup Martin , Vad-Nielsen Johan , Kjær Kathrine , Laustsen Anders , Andersen Morten N. , Rasmussen Thomas A. , Søgaard Ole S. , Østergaard Lars , Denton Paul W. , Jakobsen Martin R.
Published: April 2015

Adjunct therapy with the histone deacetylase inhibitor (HDACi) romidepsin increases plasma viremia in HIV patients on combination antiretroviral therapy (cART). However, a potential concern is that reversing HIV latency with an HDACi may reactivate the virus in anatomical compartments with suboptimal cART concentrations, leading tode novoinfection of susceptible cells in these sites. We tested physiologically relevant romidepsin concentrations known to reactivate latent HIV in order to definitively address this concern. We found that romidepsin significantly inhibited HIV infection in peripheral blood mononuclear cells and CD4+T cells but not in monocyte-derived macrophages. In addition, romidepsin impaired HIV spreading in CD4+T cell cultures. When we evaluated the impact of romidepsin on quantitative viral outgrowth assays with primary resting CD4+T cells, we found that resting CD4+T cells exposed to romidepsin exhibited reduced proliferation and viability. This significantly lowered assay sensitivity when measuring the efficacy of romidepsin as an HIV latency reversal agent. Altogether, our data indicate that romidepsin-based HIV eradication strategies are unlikely to reseed a latent T cell reservoir, even under suboptimal cART conditions, because romidepsin profoundly restrictsde novoHIV infections.
Influence of Linker Length and Composition on Enzymatic Activity and Ribosomal Binding of Neomycin Dimers
Authors: Watkins Derrick , Kumar Sunil , Green Keith D. , Arya Dev P. , Garneau-Tsodikova Sylvie
Published: April 2015

The human and bacterial A site rRNA binding as well as the aminoglycoside-modifying enzyme (AME) activity against a series of neomycin B (NEO) dimers is presented. The data indicate that by simple modifications of linker length and composition, substantial differences in rRNA selectivity and AME activity can be obtained. We tested five different AMEs with dimeric NEO dimers that were tethered via triazole, urea, and thiourea linkages. We show that triazole-linked dimers were the worst substrates for most AMEs, with those containing the longer linkers showing the largest decrease in activity. Thiourea-linked dimers that showed a decrease in activity by AMEs also showed increased bacterial A site binding, with one compound (compound 14) even showing substantially reduced human A site binding. The urea-linked dimers showed a substantial decrease in activity by AMEs when a conformationally restrictive phenyl linker was introduced. The information learned herein advances our understanding of the importance of the linker length and composition for the generation of dimeric aminoglycoside antibiotics capable of avoiding the action of AMEs and selective binding to the bacterial rRNA over binding to the human rRNA.
Role of Pseudomonas aeruginosa Low-Molecular-Mass Penicillin-Binding Proteins in AmpC Expression, β-Lactam Resistance, and Peptidoglycan Structure
Authors: Ropy Alaa , Cabot Gabriel , Sánchez-Diener Irina , Aguilera Cristian , Moya Bartolome , Ayala Juan A. , Oliver Antonio
Published: April 2015

This study aimed to characterize the role of
Pseudomonas aeruginosa
low-molecular-mass penicillin-binding proteins (LMM PBPs), namely, PBP4 (DacB), PBP5 (DacC), and PBP7 (PbpG), in peptidoglycan composition, β-lactam resistance, and
ampC
regulation. For this purpose, we constructed all single and multiple mutants of
dacB
,
dacC
,
pbpG
, and
ampC
from the wild-type
P. aeruginosa
PAO1 strain. Peptidoglycan composition was determined by high-performance liquid chromatography (HPLC),
ampC
expression by reverse transcription-PCR (RT-PCR), PBP patterns by a Bocillin FL-binding test, and antimicrobial susceptibility by MIC testing for a panel of β-lactams. Microscopy and growth rate analyses revealed no apparent major morphological changes for any of the mutants compared to the wild-type PAO1 strain. Of the single mutants, only
dacC
mutation led to significantly increased pentapeptide levels, showing that PBP5 is the major
dd
-carboxypeptidase in
P. aeruginosa
. Moreover, our results indicate that PBP4 and PBP7 play a significant role as
dd
-carboxypeptidase only if PBP5 is absent, and their
dd
-endopeptidase activity is also inferred. As expected, the inactivation of PBP4 led to a significant increase in
ampC
expression (around 50-fold), but, remarkably, the sequential inactivation of the three LMM PBPs produced a much greater increase (1,000-fold), which correlated with peptidoglycan pentapeptide levels. Finally, the β-lactam susceptibility profiles of the LMM PBP mutants correlated well with the
ampC
expression data. However, the inactivation of
ampC
in these mutants also evidenced a role of LMM PBPs, especially PBP5, in intrinsic β-lactam resistance. In summary, in addition to assessing the effect of
P. aeruginosa
LMM PBPs on peptidoglycan structure for the first time, we obtained results that represent a step forward in understanding the impact of these PBPs on β-lactam resistance, apparently driven by the interplay between their roles in AmpC induction, β-lactam trapping, and
dd
-carboxypeptidase/β-lactamase activity.
Transcriptomic Analysis of Yersinia enterocolitica Biovar 1B Infecting Murine Macrophages Reveals New Mechanisms of Extracellular and Intracellular Survival
Authors: Bent Zachary W. , Poorey Kunal , Brazel David M. , LaBauve Annette E. , Sinha Anupama , Curtis Deanna J. , House Samantha E. , Tew Karen E. , Hamblin Rachelle Y. , Williams Kelly P. , Branda Steven S. , Young Glenn M. , Meagher Robert J.
Published: April 2015

Yersinia enterocolitica
is typically considered an extracellular pathogen; however, during the course of an infection, a significant number of bacteria are stably maintained within host cell vacuoles. Little is known about this population and the role it plays during an infection. To address this question and to elucidate the spatially and temporally dynamic gene expression patterns of
Y. enterocolitica
biovar 1B through the course of an
in vitro
infection, transcriptome sequencing and differential gene expression analysis of bacteria infecting murine macrophage cells were performed under four distinct conditions. Bacteria were first grown in a nutrient-rich medium at 26°C to establish a baseline of gene expression that is unrelated to infection. The transcriptomes of these bacteria were then compared to bacteria grown in a conditioned cell culture medium at 37°C to identify genes that were differentially expressed in response to the increased temperature and medium but not in response to host cells. Infections were then performed, and the transcriptomes of bacteria found on the extracellular surface and intracellular compartments were analyzed individually. The upregulated genes revealed potential roles for a variety of systems in promoting intracellular virulence, including the Ysa type III secretion system, the Yts2 type II secretion system, and the Tad pilus. It was further determined that mutants of each of these systems had decreased virulence while infecting macrophages. Overall, these results reveal the complete set of genes expressed by
Y. enterocolitica
in response to infection and provide the groundwork for future virulence studies.
Anti-Pseudomonas aeruginosa IgY Antibodies Induce Specific Bacterial Aggregation and Internalization in Human Polymorphonuclear Neutrophils
Authors: Thomsen K. , Christophersen L. , Bjarnsholt T. , Jensen P. Ø. , Moser C. , Høiby N.
Published: April 2015

Polymorphonuclear neutrophils (PMNs) are essential cellular constituents in the innate host response, and their recruitment to the lungs and subsequent ubiquitous phagocytosis controls primary respiratory infection. Cystic fibrosis pulmonary disease is characterized by progressive pulmonary decline governed by a persistent, exaggerated inflammatory response dominated by PMNs. The principal contributor is chronic
Pseudomonas aeruginosa
biofilm infection, which attracts and activates PMNs and thereby is responsible for the continuing inflammation. Strategies to prevent initial airway colonization with
P. aeruginosa
by augmenting the phagocytic competence of PMNs may postpone the deteriorating chronic biofilm infection. Anti-
P. aeruginosa
IgY antibodies significantly increase the PMN-mediated respiratory burst and subsequent bacterial killing of
P. aeruginosa
in vitro
. The mode of action is attributed to IgY-facilitated formation of immobilized bacteria in aggregates, as visualized by fluorescence microscopy and the induction of increased bacterial hydrophobicity. Thus, the present study demonstrates that avian egg yolk immunoglobulins (IgY) targeting
P. aeruginosa
modify bacterial fitness, which enhances bacterial killing by PMN-mediated phagocytosis and thereby may facilitate a rapid bacterial clearance in airways of people with cystic fibrosis.
AP-1 Transcription Factor Serves as a Molecular Switch between Chlamydia pneumoniae Replication and Persistence
Authors: Krämer S. , Crauwels P. , Bohn R. , Radzimski C. , Szaszák M. , Klinger M. , Rupp J. , van Zandbergen G.
Published: April 2015

Chlamydia pneumoniae
is a Gram-negative bacterium that causes acute or chronic respiratory infections. As obligate intracellular pathogens, chlamydiae efficiently manipulate host cell processes to ensure their intracellular development. Here we focused on the interaction of chlamydiae with the host cell transcription factor activator protein 1 (AP-1) and its consequence on chlamydial development. During
Chlamydia pneumoniae
infection, the expression and activity of AP-1 family proteins c-Jun, c-Fos, and ATF-2 were regulated in a time- and dose-dependent manner. We observed that the c-Jun protein and its phosphorylation level significantly increased during
C. pneumoniae
development. Small interfering RNA knockdown of the c-Jun protein in HEp-2 cells reduced the chlamydial load, resulting in smaller inclusions and significantly lower chlamydial recovery. Furthermore, inhibition of the c-Jun-containing AP-1 complexes using tanshinone IIA changed the replicative infection phenotype into a persistent one. Tanshinone IIA-dependent persistence was characterized by smaller, aberrant inclusions, a strong decrease in the chlamydial load, and significantly reduced chlamydial recovery, as well as by the reversibility of the reduced recovery after the removal of tanshinone IIA. Interestingly, not only was tanshinone IIA treatment accompanied by a significant decrease of ATP levels, but fluorescence live cell imaging analysis by two-photon microscopy revealed that tanshinone IIA treatment also resulted in a decreased fluorescence lifetime of protein-bound NAD(P)H inside the chlamydial inclusion, indicating that chlamydial reticulate bodies have decreased metabolic activity. In all, these data demonstrate that the AP-1 transcription factor is involved in
C. pneumoniae
development, with tanshinone IIA treatment resulting in persistence.
Transcription of Oxidative Stress Genes Is Directly Activated by SpxA1 and, to a Lesser Extent, by SpxA2 in Streptococcus mutans
Authors: Kajfasz Jessica K. , Rivera-Ramos Isamar , Scott-Anne Kathleen , Gregoire Stacy , Abranches Jacqueline , Lemos José A.
Published: April 2015

The SpxA1 and SpxA2 (formerly SpxA and SpxB) transcriptional regulators ofStreptococcus mutansare members of a highly conserved family of proteins found inFirmicutes, and they were previously shown to activate oxidative stress responses. In this study, we showed that SpxA1 exerts substantial positive regulatory influence over oxidative stress genes following exposure to H2O2, while SpxA2 appears to have a secondary regulatory role.In vitrotranscription (IVT) assays using purified SpxA1 and/or SpxA2 showed that SpxA1 and, less often, SpxA2 directly activate transcription of some of the major oxidative stress genes. Addition of equimolar concentrations of SpxA1 and SpxA2 to the IVT reactions neither enhanced transcription of the tested genes nor disrupted the dominant role of SpxA1. Substitution of a conserved glycine residue (G52) present in both Spx proteins by arginine (SpxG52R) resulted in strains that phenocopied the Δspxstrains. Moreover, addition of purified SpxA1G52Rcompletely failed to activate transcription ofahpC,sodA, andtpx, further confirming that the G52 residue is critical for Spx functionality.

IMPORTANCEStreptococcus mutansis a pathogen associated with the formation of dental caries in humans. Within the oral cavity,S. mutansroutinely encounters oxidative stress. Our previous data revealed that two regulatory proteins, SpxA1 and SpxA2 (formerly SpxA and SpxB), bear high homology to the Spx regulator that has been characterized as a critical activator of oxidative stress genes inBacillus subtilis. In this report, we prove that Spx proteins ofS. mutansdirectly activate transcription of genes involved in the oxidative stress response, though SpxA1 appears to have a more dominant role than SpxA2. Therefore, the Spx regulators play a critical role in the ability ofS. mutansto thrive within the oral cavity.
Mediastinal mass: to resect or not to resect?
Authors: Simons Anneliese , Finnerty James , Wilson Martin
Published: April 2015

We describe a case of a 63-year-old man presenting in an acute confusional state with a markedly abnormal chest radiograph. During investigation, he developed aspiration pneumonia and was ventilated on the intensive care unit before confirming that he had autoimmune encephalopathy secondary to benign thymoma. After treatment with intravenous immunoglobulins he made an impressive recovery allowing him to be transferred to a tertiary unit for resection of the underlying mass, thus resulting in an excellent neurological recovery.
Prevalence of hypertension at high altitude: cross-sectional survey in Ladakh, Northern India 2007–2011
Authors: Norboo Tsering , Stobdan Tsering , Tsering Norboo , Angchuk Norboo , Tsering Phunsog , Ahmed Iqbal , Chorol Tsewang , Kumar Sharma Vijay , Reddy Prasanna , Singh Shashi Bala , Kimura Yumi , Sakamoto Ryota , Fukutomi Eriko , Ishikawa Motonao , Suwa Kuniaki , Kosaka Yasuyuki , Nose Mitsuhiro , Yamaguchi Takayoshi , Tsukihara Toshihiro , Matsubayashi Kozo , Otsuka Kuniaki , Okumiya Kiyohito
Published: April 2015

Objective

Prevalence of hypertension was examined in a widely dispersed (45 110 km2) representative group of Ladakhi in Northern India. The influence of hypoxic environment of wide-ranged altitude (2600–4900 m) and lifestyle change on hypertension was studied.

Methods

2800 participants (age 20–94 years) were enrolled. Systolic blood pressure ≥140 mm Hg and/or diastolic blood pressure of ≥90 mm Hg and/or taking current anti-hypertensive medicine was defined as hypertension. Height and weight for body mass index and SpO2were examined. The rural population comprised six subdivisions with a distinct altitude, dietary and occupational pattern. Participants in the urban area of Leh consist of two groups, that is, migrants settled in Leh from the Changthang nomadic area, and dwellers born in Leh. The prevalence of hypertension in the two groups was compared with that in the farmers and nomads in rural areas. The effects of ageing, hypoxia, dwelling at high altitude, obesity, modernised occupation, dwelling in an urban area, and rural-to-urban migration to hypertension were analysed by multiple logistic regression.

Results

The prevalence of hypertension was 37.0% in all participants and highest in migrants settled in Leh (48.3%), followed by dwellers born in Leh town (41.1%) compared with those in rural areas (33.5). The prevalence of hypertension in nomads (all: 27.7%, Tibetan/Ladakhi: 19.7/31.9%)) living at higher altitude (4000–4900 m) was relatively low. The associated factors with hypertension were ageing, overweight, dwelling at higher altitude, engagement in modernised sedentary occupations, dwelling in urban areas, and rural-to-urban migration. The effects of lifestyle change and dwelling at high altitude were independently associated with hypertension by multivariate analysis adjusted with confounding factors.

Conclusions

Socioeconomic and cultural factors play a big role with the effect of high altitude itself on high prevalence of hypertension in highlanders in Ladakh.
p64 Flow Modulation Device in the treatment of intracranial aneurysms: initial experience and technical aspects
Authors: Briganti Francesco , Leone Giuseppe , Marseglia Mariano , Cicala Domenico , Caranci Ferdinando , Maiuri Francesco
Published: April 2015

Background

Experience with the endovascular treatment of cerebral aneurysms by flow diverter devices (FDDs) is limited to four devices (Pipeline, Covidien; FRED, Microvention; Silk, Balt Extrusion; Surpass, Stryker), as reported in different studies.

Objective

To describe the initial experience and the technical innovations of a new-generation FDD (p64 Flow Modulation Device, Phenox, Bochum, Germany).

Methods

Between December 2014 and February 2015, six intracranial aneurysms in five patients (four women, one man; mean age 63 years) were treated with the p64 Flow Modulation Device.

Results

Immediate post-treatment angiography showed reduced flow into all aneurysms. No long-term angiographic data are available. The device may be easily deployed and totally retrieved with a unique mechanical detachment. No periprocedural technical complications occurred. No early or delayed aneurysm rupture, no ischemic or hemorrhagic complications, and no neurological morbidity or death were seen.

Conclusions

Treatment of cerebral aneurysms with the p64 Flow Modulation Device is a safe procedure with no technical complications. The mechanical detachment and the 100% retrievability are significant advantages of this new device. However, large prospective studies with long-term clinical and angiographic follow-up are necessary to assess the role of the p64 in the endovascular treatment of intracranial aneurysms.
Dietary intake habits and controlled training on body composition and strength in elite female volleyball players during the season
Authors: Mielgo-Ayuso Juan , Zourdos Michael C. , Calleja-González Julio , Urdampilleta Aritz , Ostojic Sergej M.
Published: April 2015

The purpose of this study was to assess dietary intake of elite female volleyball players (EFVPs, n = 22) during the first 11 weeks of the competitive season. Further, we compared findings for total energy intake and specific macronutrient distribution with the established recommendations for high-intensity athletes. Subjects also engaged in periodized training and we assessed changes in body composition (BC) and strength. Twenty-two EFVPs had dietary intake (7-day dietary recall and food-frequency questionnaire), BC (body mass index (BMI), body fat percentage, fat mass, muscle mass), and 1-repetition maximum (1RM) strength (bench press, military press, back squat, power clean, clean and jerk, pull-over) assessed at baseline (T0, before preseason) and 11 weeks later (T11). Athletes consumed less total kilocalories and carbohydrates (CHO) compared with established recommendations (total kilocalories: 40.7 ± 5.2 kcal/(kg·day)–1 vs. recommendations: 50–80 kcal/(kg·day)–1; CHO: 4.3 ± 0.6 g/(kg·day)–1 vs. recommendations: 5–8 g/(kg·day)–1). Further, subjects consumed greater protein (2.1 ± 0.4 g/(kg·day)–1) compared with recommendations (1.6–1.8 g/(kg·day)–1) and greater fat (36.1 ± 4.6% of total kilocalories) than recommendations (20%–35% of total kilocalories). There were improvements (p < 0.05) in BC from T0–T11 (body fat percentage: 17.9% ± 4.2%–16.8% ± 3.6%, –4.7% ± 7.4%; fat mass: 12.7 ± 4.2–11.9 ± 3.8 kg, –4.0% ± 9.2%; muscle mass: 42.8% ± 3.4%–43.3% ± 3.0%, +1.3 ± 3.1%) and 1RM strength (bench press: 39.1 ± 4.5–43.4 ± 4.9 kg; +11.4% ± 9.3%; clean and jerk: 29.7 ± 6.3–34 ± 5.8 kg; +17.7% ± 23.8%); however, there was no change (p > 0.05) in BMI or military press and pull-over. Back squat (p = 0.054; +33.0% ± 83.7%) and power clean (p = 0.056; +26.2% ± 49.0%) increases approached significance. Our findings indicate that EFVPs improved BC and strength despite a dietary intake different from recommendations. This is possibly due to different substrate utilization during exercise in females versus males, thus new recommendations should be considered for high-intensity athletes, which are sex-specific.
Intense rockburst impacts in deep underground construction and their prevention
Authors: Mazaira A. , Konicek P.
Published: April 2015

In the last few decades, in both mining and civil engineering projects, deeper excavations have been carried out than in the past. With this increase in depth, rocks may overstress and rock failures can occur during excavation. When competent rock strata are encountered under high stress conditions, these failures can vary from superficial spalling to explosive rockburst. Intense rockbursts may cause fatal injuries to workers and significant loss of equipment and time. The occurrence of rockbursts is always difficult to predict and special steps and measures must be taken to control them. First, burst-prone zones must be predicted by an early exhaustive geological study and by the assessment of in situ stress level and orientation. Second, basic design parameters, e.g., shape, size, and excavation method, should be modified and adapted to the expected conditions to minimize rockburst risk. Third, in situ pre-conditioning methods, e.g., destress blasting, can be applied to decrease the capacity of the rock mass to store energy. Finally, special rock support and reinforcement systems, i.e., yielding systems, must be installed after excavation to ensure total stability of the opening. This paper reviews the geological and geomechanical factors that provoke and influence rockbursts in overstressed rock masses and the engineering measures taken to control them.