bluuebunny/crossref_metadata_2025 huggingface dataset:
In Vitro
Activity of Aztreonam-Avibactam against Enterobacteriaceae and Pseudomonas aeruginosa Isolated by Clinical Laboratories in 40 Countries from 2012 to 2015
Authors: Karlowsky James A. , Kazmierczak Krystyna M. , de Jonge Boudewijn L. M. , Hackel Meredith A. , Sahm Daniel F. , Bradford Patricia A.
Published: June 2017

The combination of the monobactam aztreonam and the non-β-lactam β-lactamase inhibitor avibactam is currently in clinical development for the treatment of serious infections caused by metallo-β-lactamase (MBL)-producing
Enterobacteriaceae
, a difficult-to-treat subtype of carbapenem-resistant
Enterobacteriaceae
for which therapeutic options are currently very limited. The present study tested clinically significant isolates of
Enterobacteriaceae
(
n
= 51,352) and
Pseudomonas aeruginosa
(
n
= 11,842) collected from hospitalized patients in 208 medical center laboratories from 40 countries from 2012 to 2015 for
in vitro
susceptibility to aztreonam-avibactam, aztreonam, and comparator antimicrobial agents using a standard broth microdilution methodology. Avibactam was tested at a fixed concentration of 4 μg/ml in combination with 2-fold dilutions of aztreonam. The MIC
90
s of aztreonam-avibactam and aztreonam were 0.12 and 64 μg/ml, respectively, for all
Enterobacteriaceae
isolates; >99.9% of all isolates and 99.8% of meropenem-nonsusceptible isolates (
n
= 1,498) were inhibited by aztreonam-avibactam at a concentration of ≤8 μg/ml. PCR and DNA sequencing identified 267
Enterobacteriaceae
isolates positive for MBL genes (NDM, VIM, IMP); all
Enterobacteriaceae
carrying MBLs demonstrated aztreonam-avibactam MICs of ≤8 μg/ml and a MIC
90
of 1 μg/ml. Against all
P. aeruginosa
isolates tested, the MIC
90
of both aztreonam-avibactam and aztreonam was 32 μg/ml; against MBL-positive
P. aeruginosa
isolates (
n
= 452), MIC
90
values for aztreonam-avibactam and aztreonam were 32 and 64 μg/ml, respectively. The current study demonstrated that aztreonam-avibactam possesses potent
in vitro
activity against a recent, sizeable global collection of
Enterobacteriaceae
clinical isolates, including isolates that were meropenem nonsusceptible, and against MBL-positive isolates of
Enterobacteriaceae
, for which there are few treatment options.
Occurrence of Clinically Important Lineages, Including the Sequence Type 131 C1-M27 Subclone, among Extended-Spectrum-β-Lactamase-Producing Escherichia coli in Wastewater
Authors: Gomi Ryota , Matsuda Tomonari , Matsumura Yasufumi , Yamamoto Masaki , Tanaka Michio , Ichiyama Satoshi , Yoneda Minoru
Published: June 2017

Contamination of environmental waters by extended-spectrum-β-lactamase (ESBL)-producing
Escherichia coli
(ESBLEC) is of great concern. Wastewater treatment plants (WWTPs) and hospitals release large amounts of ESBLEC into the environment. In the present study, we isolated ESBLEC strains from wastewater collected from a WWTP and a hospital in Japan and performed whole-genome sequencing to characterize these strains. Genomic analysis of 54 strains (32 from the WWTP and 22 from hospital wastewater) revealed the occurrence of clinically important clonal groups with extraintestinal pathogenic
E. coli
status in the WWTP and hospital wastewater. Fine-scale phylogenetic analysis was performed to further characterize 15 sequence type 131 (ST131) complex strains (11 from the WWTP and 4 from hospital wastewater). These ST131 complex strains were comprised of the following different subgroups: clade A (
n
= 2), C1-M27 (
n
= 8), and C1 (non-C1-M27) (
n
= 1) for strains from the WWTP and clade A (
n
= 2), C1-M27 (
n
= 1), and C1 (non-C1-M27) (
n
= 1) for strains from hospital wastewater. The results indicate that ESBLEC strains belonging to clinically important lineages, including the C1-M27 clade, may disseminate into the environment through wastewater, highlighting the need to monitor for antibiotic resistance in wastewater.
Bactericidal and Sterilizing Activity of a Novel Regimen with Bedaquiline, Pretomanid, Moxifloxacin, and Pyrazinamide in a Murine Model of Tuberculosis
Authors: Li Si-Yang , Tasneen Rokeya , Tyagi Sandeep , Soni Heena , Converse Paul J. , Mdluli Khisimuzi , Nuermberger Eric L.
Published: June 2017

New regimens based on 2 or more novel agents are sought to shorten or to simplify treatment of tuberculosis (TB), including drug-resistant forms. Prior studies showed that the novel combinations of bedaquiline (BDQ) plus pretomanid (PMD) plus pyrazinamide (PZA) and PMD plus moxifloxacin (MXF) plus PZA shortened the treatment duration necessary to prevent relapse by 2 to 3 months and 1 to 2 months, respectively, compared with the current first-line regimen, in a murine TB model. These 3-drug combinations are now being studied in clinical trials. Here, the 4-drug combination of BDQ+PMD+MXF+PZA was compared to its 3-drug component regimens and different treatment durations of PZA and MXF were explored, to identify the optimal regimens and treatment times and to estimate the likelihood of success against drug-resistant strains. BDQ+PMD+MXF+PZA rendered all mice relapse-free after 2 months of treatment. PZA administration could be discontinued after the first month of treatment without worsening outcomes, whereas the absence of MXF, PZA, or BDQ administration from the beginning necessitated approximately 0.5, 1, or 2 months, respectively, of additional treatment to attain the same outcome.
Listeria-Vectored Vaccine Expressing the Mycobacterium tuberculosis 30-Kilodalton Major Secretory Protein via the Constitutively Active
prfA
* Regulon Boosts Mycobacterium bovis BCG Efficacy against Tuberculosis
Authors: Jia Qingmei , Dillon Barbara Jane , Masleša-Galić Saša , Horwitz Marcus A.
Published: June 2017

A potent vaccine against tuberculosis, one of the world's deadliest diseases, is needed to enhance the immunity of people worldwide, most of whom have been vaccinated with the partially effective
Mycobacterium bovis
BCG vaccine. Here we investigate novel live attenuated recombinant
Listeria monocytogenes
(rLm) vaccines expressing the
Mycobacterium tuberculosis
30-kDa major secretory protein (r30/antigen 85B [Ag85B]) (rLm30) as heterologous booster vaccines in animals primed with BCG. Using three attenuated
L. monocytogenes
vectors,
L. monocytogenes
Δ
actA
(LmI),
L. monocytogenes
Δ
actA
Δ
inlB
(LmII), and
L. monocytogenes
Δ
actA
Δ
inlB prfA
* (LmIII), we constructed five rLm30 vaccine candidates expressing r30 linked in frame to the
L. monocytogenes
listeriolysin O signal sequence and driven by the
hly
promoter (h30) or linked in frame to the ActA N-terminal 100 amino acids and driven by the
actA
promoter (a30). All five rLm30 vaccines secreted r30 in broth and macrophages; while rLm30 expressing r30 via a constitutively active
prfA
* regulon (rLmIII/a30) expressed the largest amount of r30 in broth culture, all five rLm30 vaccines expressed equivalent amounts of r30 in infected macrophages. In comparative studies, boosting of BCG-immunized mice with rLmIII/a30 induced the strongest antigen-specific T-cell responses, including splenic and lung polyfunctional CD4
+
T cells expressing the three cytokines interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), and interleukin-2 (IL-2) (
P
< 0.001) and splenic and lung CD8
+
T cells expressing IFN-γ (
P
< 0.0001). In mice and guinea pigs, the rLmIII/a30 and rLmI/h30 vaccines were generally more potent booster vaccines than r30 with an adjuvant and a recombinant adenovirus vaccine expressing r30. In a setting in which BCG alone was highly immunoprotective, boosting of mice with rLmIII/a30, the most potent of the vaccines, significantly enhanced protection against aerosolized
M. tuberculosis
(
P
< 0.01).
Ehrlichia chaffeensis TRP120 Moonlights as a HECT E3 Ligase Involved in Self- and Host Ubiquitination To Influence Protein Interactions and Stability for Intracellular Survival
Authors: Zhu Bing , Das Seema , Mitra Shubhajit , Farris Tierra R. , McBride Jere W.
Published: June 2017

Ehrlichia chaffeensis
secretes tandem repeat protein (TRP) effectors that are involved in a diverse array of host cell interactions, some of which directly activate cell signaling pathways and reprogram host gene transcription to promote survival in the mononuclear phagocyte. However, the molecular details of these effector-host interactions and roles in pathobiology are incompletely understood. In this study, we determined that the
E. chaffeensis
effector TRP120 is posttranslationally modified by ubiquitin (Ub) and that ubiquitination occurs through intrinsic and host-mediated HECT ligase activity. A functional HECT E3 ligase domain with a conserved catalytic site was identified in the C-terminal region of TRP120, and TRP120 autoubiquitination occurred
in vitro
in the presence of host UbcH5b/c E2 enzymes. TRP120 ubiquitination sites were mapped using a high-density microfluidic peptide array and confirmed by ectopic expression of TRP120 lysine mutants in cells. Moreover, we determined that the HECT E3 ubiquitin ligase, Nedd4L, interacts with TRP120 during infection and also mediates TRP120 ubiquitination. Nedd4L knockdown resulted in the reduction of TRP120-Ub, decreased ehrlichial infection, and reduced recruitment of a known TRP120-interacting host protein, PCGF5, to ehrlichial inclusions. TRP120-mediated PCGF5 polyubiquitination was associated with a reduction in PCGF5 levels. Inhibition of ubiquitination with small molecules also significantly decreased ehrlichial infection, indicating that the Ub pathway is critical for ehrlichial intracellular replication and survival. The current study identified a novel
E. chaffeensis
ubiquitin ligase and revealed an important role for the ubiquitin pathway in effector-host interactions and pathogen-mediated host protein stability in order to promote intracellular survival.
Absence of the Polar Organizing Protein PopZ Results in Reduced and Asymmetric Cell Division in Agrobacterium tumefaciens
Authors: Howell Matthew , Aliashkevich Alena , Salisbury Anne K. , Cava Felipe , Bowman Grant R. , Brown Pamela J. B.
Published: June 2017

Agrobacterium tumefaciensis a rod-shaped bacterium that grows by polar insertion of new peptidoglycan during cell elongation. As the cell cycle progresses, peptidoglycan synthesis at the pole ceases prior to insertion of new peptidoglycan at midcell to enable cell division. TheA. tumefacienshomolog of theCaulobacter crescentuspolar organelle development protein PopZ has been identified as a growth pole marker and a candidate polar growth-promoting factor. Here, we characterize the function of PopZ in cell growth and division ofA. tumefaciens. Consistent with previous observations, we observe that PopZ localizes specifically to the growth pole in wild-type cells. Despite the striking localization pattern of PopZ, we find the absence of the protein does not impair polar elongation or cause major changes in the peptidoglycan composition. Instead, we observe an atypical cell length distribution, including minicells, elongated cells, and cells with ectopic poles. Most minicells lack DNA, suggesting a defect in chromosome segregation. Furthermore, the canonical cell division proteins FtsZ and FtsA are misplaced, leading to asymmetric sites of cell constriction. Together, these data suggest that PopZ plays an important role in the regulation of chromosome segregation and cell division.

IMPORTANCEA. tumefaciensis a bacterial plant pathogen and a natural genetic engineer. However, very little is known about the spatial and temporal regulation of cell wall biogenesis that leads to polar growth in this bacterium. Understanding the molecular basis ofA. tumefaciensgrowth may allow for the development of innovations to prevent disease or to promote growth during biotechnology applications. Finally, since many closely related plant and animal pathogens exhibit polar growth, discoveries inA. tumefaciensmay be broadly applicable for devising antimicrobial strategies.
Communal Metabolism of Methane and the Rare Earth Element Switch
Authors: Yu Zheng , Chistoserdova Ludmila
Published: June 2017

The metabolism of methane is an important part of the biogeochemical cycling of carbon. Methane is also a major contributor to climate change. A specialized group of microbes that consume methane, the methanotrophs, represent a natural filter preventing even faster accumulation of methane in the atmosphere. Methanotrophy can proceed via both anaerobic and aerobic modes. The anaerobic methanotrophs, represented by both archaea and bacteria, all appear to be engaged in syntrophic interdependencies with other species, to overcome the energetic barriers of methane metabolism in the absence of oxygen. In contrast, aerobic methanotrophy can be carried out by pure cultures of bacteria. However, a concept of communal function in aerobic methane oxidation has been gaining momentum, based on data regarding the natural cooccurrence of specific functional guilds and results from laboratory manipulations. The mechanistic details of how and why the methanotrophs share their carbon with other species, and whether and what they gain in return, are still sparse. In this minireview, we highlight recent studies that led to this new concept of community function in aerobic methane oxidation. We first describe stable isotope probing experiments employing heavy-carbon-labeled methane and tracing methane carbon consumption. We then present an analysis of data on microcosm community dynamics. We further discuss the role of a synthetic community approach in elucidating the principles of carbon flow and species cooperation in methane consumption. Finally, we touch on the role of lanthanides, which are rare Earth elements previously thought to be biologically inert, in bacterial metabolism of methane.
Psychosocial therapy for Parkinson's-related dementia: study protocol for the INVEST randomised controlled trial
Authors: McCormick Sheree A , McDonald Kathryn R , Vatter Sabina , Orgeta Vasiliki , Poliakoff Ellen , Smith Sarah , Silverdale Monty A , Fu Bo , Leroi Iracema
Published: June 2017

Introduction

Parkinson's disease (PD) with mild cognitive impairment (MCI-PD) or dementia (PDD) and dementia with Lewy bodies (DLB) are characterised by motor and ‘non-motor’ symptoms which impact on quality of life. Treatment options are generally limited to pharmacological approaches. We developed a psychosocial intervention to improve cognition, quality of life and companion burden for people with MCI-PD, PDD or DLB. Here, we describe the protocol for a single-blind randomised controlled trial to assess feasibility, acceptability and tolerability of the intervention and to evaluate treatment implementation. The interaction among the intervention and selected outcome measures and the efficacy of this intervention in improving cognition for people with MCI-PD, PDD or DLB will also be explored.

Methods and analysis

Dyads will be randomised into two treatment arms to receive either ‘treatment as usual’ (TAU) or cognitive stimulation therapy specifically adapted for Parkinson's-related dementias (CST-PD), involving 30 min sessions delivered at home by the study companion three times per week over 10 weeks. A mixed-methods approach will be used to collect data on the operational aspects of the trial and treatment implementation. This will involve diary keeping, telephone follow-ups, dyad checklists and researcher ratings. Analysis will include descriptive statistics summarising recruitment, acceptability and tolerance of the intervention, and treatment implementation. To pilot an outcome measure of efficacy, we will undertake an inferential analysis to test our hypothesis that compared with TAU, CST-PD improves cognition. Qualitative approaches using thematic analysis will also be applied. Our findings will inform a larger definitive trial.

Ethics and dissemination

Ethical opinion was granted (REC reference: 15/YH/0531). Findings will be published in peer-reviewed journals and at conferences. We will prepare reports for dissemination by organisations involved with PD and dementia.

Trial registration number

ISRCTN (ISRCTN11455062).
Assessment of dysphotopsia in pseudophakic subjects with multifocal intraocular lenses
Authors: Buckhurst Phillip J , Naroo Shehzad A , Davies Leon N , Shah Sunil , Drew Tom , Wolffsohn James S
Published: June 2017

Aim

To better understand the phenomenon of dysphotopsia in patients implanted with multifocal intraocular lenses (IOLs).

Methods

Forty-five patients (aged 61.8±8.9 years) implanted bilaterally with Tecnis ZM900 (diffractive multifocal), Lentis Mplus MF30 (segmented refractive multifocal) or Softec-1 (monofocal) IOLs (each n=15) 4–6 months previously and who had achieved a good surgical outcome were examined. Each reported their dysphotopsia symptoms subjectively, identified its form (EyeVisPod illustrations), quantified retinal straylight (C-Quant) and halo perception (Aston halometer). Retinal straylight and halometry was repeated by a second masked clinician to determine interobserver repeatability.

Results

Subjective dysphotopsia ratings were able to differentiate Tecnis ZM900 from Lentis Mplus MF30 (p<0.001), but not Lentis Mplus MF30 from groups implanted with Softec-1 (p=0.290). Straylight was similar between the monofocal and multifocal IOL designs (p=0.664). ZM900 IOLs demonstrated a uniform increase in dysphotopsia in comparison with the monofocal IOL (p<0.001) as measured with the halometer, whereas sectorial refractive multifocal IOLs demonstrated a localised increase in dysphotopsia over the inferior visual field. Intraobserver repeatability was good for the straylight (intraclass correlation coefficients (ICC)=0.77) and halometry (ICC=0.89). There was no significant correlation between the subjective dysphotopsia severity and the straylight (p=0.503) or halometry (p>0.10) quantification or between straylight and the halo area (p>0.30).

Conclusions

Multifocal IOLs induce symptoms of dysphotopsia. Straylight did not differentiate between IOL designs, however halometry identified clear differences in light scatter due to the IOL optics. Whereas, subjective rating of overall dysphotopsia are not strongly associated with straylight or halo perception, the halometry polar diagram reflected the subjective descriptions of dysphotopsia.
Investigation of thermal and optical properties of some quartet mixed hydrogen-bonded liquid crystals
Authors: Okumuş Mustafa
Published: June 2017

In this study, the thermal and optical properties of quartet mixtures formed at different weight ratios (1:1:1:1 and 1.5:1:1:1) from liquid crystals 4-octyloxy-4[Formula: see text]-cyanobiphenyl (8OCB), 4-hexylbenzoic acid, 4-(octyloxy)benzoic acid and 4-(decyloxy)benzoic acid were investigated by differential scanning calorimeter (DSC) and polarized optic microscopy (POM). The phase transition temperatures of the novel quartet mixtures measured in the DSC experiments are in line with the POM experiments. The experimental results clearly show that the novel liquid crystal mixtures have displayed pure liquid crystalline properties. According to the phase diagram drawn from DSC results, the nematic range of the novel mixture at the eutectic point is larger than the nematic ranges of the components. The mesomorphic structures of produced homolog complex mixtures are found to be smectic and nematic phases. But the smectic phase cannot be observed in the novel complex 1.5:1:1:1 mixture during continuous cooling. The nematic range of the novel complex 1.5:1:1:1 mixture is bigger than the nematic range of the novel complex 1:1:1:1 mixture with increasing 8OCB. Also, the nematic-to-isotropic phase transition temperature decreases with increasing the weight ratio of 8OCB in the complex quartet mixture. Another interesting result is that the produced mixtures are to be like a medical cream at room temperatures. Furthermore, order parameter and thermal stability factor of the transitions are also calculated.
Characteristic analysis of a photoexcited metamaterial perfect absorber at terahertz frequencies
Authors: Bing Pibin , Huang Shichao , Li Zhongyang , Yu Zhou , Lu Ying , Yao Jianquan
Published: June 2017

The absorption characteristics of a photoexcited metamaterial absorber at terahertz frequencies were analyzed in this study. Filling photosensitive semiconductor silicon into the gap between the resonator arms leads to modulation of its electromagnetic response through a pump beam which changes conductivity of silicon. Comparisons of terahertz absorbing properties which were caused by different thicknesses and dielectric constants of polyimide, cell sizes and widths of SRRs, and lengths and conductivities of the photosensitive silicon, were studied by using Finite Difference Time Domain (FDTD) from 0.4 THz to 1.6 THz. The results of this study will facilitate the design and preparation of terahertz modulator, filters and absorbers.
On the vibrational characteristics of single-walled boron nitride nanotubes/polymer nanocomposites: A finite element simulation
Authors: Rouhi S. , Ansari R. , Nikkar A.
Published: June 2017

The finite element method is used here to investigate the vibrational behavior of single-walled boron nitride nanotube/polymer nanocomposites. The polymer matrix is modeled as a continuous media. Besides, nanotubes are modeled as a space-frame structure. It is shown that increasing the length of nanotubes at a constant volume fraction leads to decreasing of the nanocomposite frequency. By investigating the effect of volume percentage on the frequencies of the boron nitride nanotube-reinforced polymer nanocomposites, it is observed that for short nanotubes, the nanocomposites with larger nanotube volume fractions have larger frequencies. Also, through studying the first 10 frequencies of nanocomposites reinforced by armchair and zigzag nanotubes, it is shown that the effect of chirality on the vibrational behavior of nanocomposite is insignificant.
Controlling heat transport in the spin-chain system with multi-spin interaction and external field
Authors: Zhang Xiu-Xing , Zhang Guo-Wen
Published: June 2017

The heat currents and thermal rectification in a non-equilibrium spin-chain system with multi-spin interaction and external field are investigated. The influence of system parameters, including mean temperature, temperature difference, external field and multi-spin interaction, on heat currents and thermal rectification are studied. We show that the magnitude of heat currents and thermal rectification can be controlled by varying these parameters. Particularly, by increasing the intensity of multi-spin interaction and external field, two kinds of blockade phenomena can be observed, i.e. the thermal blockade and the energy blockade. Besides, the physical origin of thermal rectification and the blockade phenomena are explored. In addition, the present results may provide a useful approach to the controlling of heat currents when there exists multi-spin interaction in the system.
Gravitational time dilation induced decoherence in spontaneous emission
Authors: Xie Dong , Xu Chunling , Wang An Min
Published: June 2017

We investigate decoherence of quantum superpositions induced by gravitational time dilation and spontaneous emission between two atomic levels. It has been shown that gravitational time dilation can be a universal decoherence source by Pikovski et al. Here, we consider the decoherence induced by the gravitational time dilation only in the situation of spontaneous emission. We obtain the analytical results of the coherence of particle’s position state. Then, we obtain that the coherence of particle’s position state depends on reference frame because the time dilation changes the distinguishability of emitted photons from two positions of particle in different reference frames. For observing the decoherence effect induced by the gravitational time dilation, time-delayed feedback can be utilized to increase the decoherence of particle’s superposition state.
KNOWLEDGE FLOW, INNOVATIVE CAPABILITIES AND BUSINESS SUCCESS: PERFORMANCE OF THE RELATIONSHIP BETWEEN SMALL WORLD NETWORKS TO PROMOTE INNOVATION
Authors: SINGH NITYA PRASAD , STOUT BLAINE DAVID
Published: June 2017

The question of how innovation comes about, and the circumstances under which it prospers, is a question that has continued to be the focus of academic research on innovation creation. Recent works have focused on how the capacity to innovate hinges on the ability to form networks; hence, the importance of the research. The article therefore answers the research question of whether the network relationships between similar ethnic, education background, and geographically clustered groups plays a significant role in innovation creation or not? Using the theoretical concept of a Small World Network, we use case study methodology to study the origins of several companies from the technology sector, who in recent years have emerged as successful businesses. The article examines the small world network dimensions of ethnicity, education, geography and the binding subject matter interest that initially formed these relationships, as well as the impact that these relationships have on innovation creation and business success.
India and Antarctica in the Precambrian: a brief analysis
Authors: Meert Joseph G. , Pandit Manoj K. , Pivarunas Anthony , Katusin Karastin , Sinha Anup K.
Published: June 2017

In this short paper, we outline the potential links between India and the East Antarctica region from Enderby Land to Princess Elizabeth Land using the Mesozoic East Gondwana configuration as a starting point. Palaeomagnetic data indicate that East Gondwana did not exist prior to the Ediacaran–Cambrian. Early Neoproterozoic (1050–950 Ma) deformation in East Antarctica and along the Eastern Ghats Province in India marks the initial contact between the two regions. Volcanism in the Kerguelen hotspot led to final break-up of India and East Antarctica in the Cretaceous. Although connections between the Archaean and Proterozoic provinces of India and East Antarctica have been proposed, the current record of large igneous provinces (or dyke swarms), palaeomagnetic data and geochronology do not show a consistently good match between the two regions.
Fatty Acid Profiles of Stipe and Blade from the Norwegian Brown MacroalgaeLaminaria hyperboreawith Special Reference to Acyl Glycerides, Polar Lipids, and Free Fatty Acids
Authors: Foseid Lena , Devle Hanne , Stenstrøm Yngve , Naess-Andresen Carl Fredrik , Ekeberg Dag
Published: June 2017

A thorough analysis of the fatty acid profiles of stipe and blade from the kelp speciesLaminaria hyperboreais presented. Lipid extracts were fractionated into neutral lipids, free fatty acids, and polar lipids, prior to derivatization and GC-MS analysis. A total of 42 fatty acids were identified and quantified, including then-3 fatty acidsα-linolenic acid, stearidonic acid, and eicosapentaenoic acid. The fatty acid amounts are higher in blade than in stipe (7.42 mg/g dry weight and 2.57 mg/g dry weight, resp.). The highest amounts ofn-3 fatty acids are found within the neutral lipid fractions with 590.6 ug/g dry weight and 100.9 ug/g dry weight for blade and stipe, respectively. The amounts of polyunsaturated fatty acids are 3.4 times higher in blade than stipe. The blade had the highest PUFA/SFA ratio compared to stipe (1.02 versus 0.76) and the lowestn-6/n-3 ratio (0.8 versus 3.5). This study highlights the compositional differences between the lipid fractions of stipe and blade fromL. hyperborea. The amount of polyunsaturated fatty acids compared to saturated- and monounsaturated fatty acids is known to influence human health. In the pharmaceutical, food, and feed industries, this can be of importance for production of different health products.
Maximum Principle for Forward‐Backward Control System Driven by Itô‐Lévy Processes under Initial‐Terminal Constraints
Authors: Liu Meijuan , Wang Xiangrong , Huang Hong
Published: June 2017

This paper investigates a stochastic optimal control problem where the control system is driven by Itô‐Lévy process. We prove the necessary condition about existence of optimal control for stochastic system by using traditional variational technique under the assumption that control domain is convex. We require that forward‐backward stochastic differential equations (FBSDE) be fully coupled, and the control variable is allowed to enter both diffusion and jump coefficient. Moreover, we also require that the initial‐terminal state be constrained. Finally, as an application to finance, we show an example of recursive consumption utility optimization problem to illustrate the practicability of our result.
Treatment of Nonclassic 11-Hydroxylase Deficiency with Ashwagandha Root
Authors: Powell Daniel , Inoue Taiga , Bahtiyar Gül , Fenteany Gabriel , Sacerdote Alan
Published: June 2017

An elderly woman presented with acne and male pattern alopecia, which upon diagnostic evaluation was found to be due to nonclassic 11-hydroxylase deficiency. We previously reported that Ashwagandha root ameliorates nonclassic 3-β-ol dehydrogenase and aldosterone synthase deficiencies. This is the first report of its use being associated with amelioration of nonclassic 11-hydroxylase deficiency, where its apparent effects appear to be dose-related.
Development of New Deep Venous Thrombosis While on Apixaban
Authors: Sharma Munish , Ramanathan Sabarina , Khalighi Koroush
Published: June 2017

The efficacy of novel oral anticoagulants (NOACs) in preventing deep venous thrombosis (DVT) has been established in large multicenter trials. Predictable pharmacokinetics, avoidance of routine laboratory monitoring, and lesser drug interactions have made NOACs safer and more tolerable treatment option in comparison to warfarin. However, cases of treatment failure mainly due to interindividual variation in plasma drug levels can be seen rarely. In this report we describe a case of acute DVT of right lower extremity in a patient who was on apixaban for prevention of venous thromboembolism (VTE) due to underlying nonvalvular atrial fibrillation (NVAF).
Diarrhea as a Presenting Symptom of Disseminated Toxoplasmosis
Authors: Glover Matthew , Tang Zhouwen , Sealock Robert , Jain Shilpa
Published: June 2017

Disseminated toxoplasmosis is uncommon in both immunocompetent and immunocompromised hosts with gastrointestinal involvement being rarely described. We report a case of disseminated gastrointestinal toxoplasmosis in an immunocompromised man who presented with one month of diarrhea and abdominal pain. Imaging showed thickening of the ascending colon and cecum. Esophagogastroduodenoscopy and colonoscopy biopsies revealedToxoplasma gondii, confirmed by immunostain. Symptoms completely resolved following treatment with pyrimethamine, sulfadiazine, and leucovorin. This case highlights the importance of including toxoplasmosis in the differential diagnosis of any immunocompromised individual presenting with gastrointestinal symptoms.
Resin Nanoceramic CAD/CAM Restoration of the Primary Molar: 3-Year Follow-Up Study
Authors: Demirel Akif , Bezgin Tuğba , Akaltan Funda , Sarı Şaziye
Published: June 2017

This case report presents the clinical use of a resin nanoceramic CAD/CAM restoration of a primary second molar without successor in the form of a permanent second premolar tooth in a patient. Three-year follow-up of the case revealed that resin nanoceramic CAD/CAM restoration of the primary molar without successor achieved both aesthetics and function. Despite the high cost of treatment, this type of restoration should be considered if the retained tooth is expected to maintain functionality over the long term.
Cynanchum wilfordii Polysaccharides Suppress Dextran Sulfate Sodium-Induced Acute Colitis in Mice and the Production of Inflammatory Mediators from Macrophages
Authors: Cho Chang-Won , Ahn Sungeun , Lim Tae-Gyu , Hong Hee-Do , Rhee Young Kyoung , Yang Deok-Chun , Jang Mi
Published: June 2017

We recently reported the immune-enhancing effects of a high-molecular-weight fraction (HMF) of CW in macrophages and immunosuppressed mice, and this effect was attributed to a crude polysaccharide. As polysaccharides may also have anti-inflammatory functions, we investigated the anti-inflammatory effects and related molecular mechanisms of a crude polysaccharide (HMFO) obtained from HMF of CW in mice with dextran sulfate sodium- (DSS-) induced colitis and in lipopolysaccharide-induced RAW 264.7 macrophages. HMFO ameliorated the pathological characteristics of colitis and significantly reduced production of proinflammatory cytokines in the serum. Histological analysis indicated that HMFO improved the signs of histological damage such as abnormal crypts, crypt loss, and inflammatory cell infiltration induced by DSS. In addition, HMFO inhibited iNOS and COX-2 protein expression, as well as phosphorylated NF-κB p65 levels in the colon tissue of mice with DSS-induced colitis. In macrophages, HMFO inhibited several cytokines and enzymes involved in inflammation such as prostaglandin E2, nitric oxide, tumor necrosis factor-α, interleukin-6, inducible nitric oxide synthase, and cyclooxygenase-2 by attenuating nuclear factor-κB (NF-κB) and mitogen-activated protein kinases. HMFO attenuated inflammation both in vitro and in vivo, primarily by inhibiting NF-κB activation. Our findings indicate that HMFO is a promising remedy for treating inflammatory bowel diseases, such as colitis.
Entropy and Selection: Life as an Adaptation for Universe Replication
Authors: Price Michael E.
Published: June 2017

Natural selection is the strongest known antientropic process in the universe when operating at the biological level and may also operate at the cosmological level. Consideration of how biological natural selection creates adaptations may illuminate the consequences and significance of cosmological natural selection. An organismal trait is more likely to constitute an adaptation if characterized by more improbable complex order, and such order is the hallmark of biological selection. If the same is true of traits created by selection in general, then the more improbably ordered something is (i.e., the lower its entropy), the more likely it is to be a biological or cosmological adaptation. By this logic, intelligent life (as the least-entropic known entity) is more likely than black holes or anything else to be an adaptation designed by cosmological natural selection. This view contrasts with Smolin’s suggestion that black holes are an adaptation designed by cosmological natural selection and that life is the by-product of selection for black holes. Selection may be the main or only ultimate antientropic process in the universe/multiverse; that is, much or all observed order may ultimately be the product or by-product of biological and cosmological selection.
Autologous Concentrated Bone Marrow Grafting for the Treatment of Osteonecrosis of the Humeral Head: A Report of Five Shoulders in Four Cases
Authors: Makihara Takeshi , Yoshioka Tomokazu , Sugaya Hisashi , Yamazaki Masashi , Mishima Hajime
Published: June 2017

Five shoulders in four patients affected by advanced osteonecrosis of the humeral head were treated with autologous concentrated bone marrow grafting. Bone marrow sample was aspirated from the iliac crests, concentrated by a centrifugation technique, and injected into the necrotic site. The shoulders were evaluated radiologically with X-ray scoring and clinically with measurement of range of motion and pain score (visual analogue scale, VAS). The mean follow-up period was 49.4 (range, 24–73) months. The concentration ratio of nucleated cells was calculated and the number of transplanted mesenchymal stem cells (MSC) was estimated by a colony-forming assay. All four shoulders with stage 3 disease achieved joint sparing. One shoulder with stage 4 disease required replacement surgery. Clinical evaluation of the spared joints showed improvement in range of motion in two cases and deterioration in two cases. VAS scores were 0 after surgery in three cases. The mean concentration ratio was 2.73, and the mean number of transplanted MSC was 1125. The outcomes of autologous concentrated bone marrow grafting for advanced osteonecrosis of the humeral head were varied. Further research is needed to determine the effectiveness and the indications of the present surgery.
An Image Restoration Method Using Matrix Transform and Gaussian Mixture Model for Radio Tomographic Imaging
Authors: Gao Fei , Sun Cheng , Liu Heng , An Jianping , Xu Shengxin
Published: June 2017

Radio Tomographic Imaging (RTI) is an attractive technique for imaging the nonmetallic targets within wireless sensor network. RTI has been used in many challenging environments and situations. Due to the accuracy of Radio Tomographic Imaging system model and the interference between the wireless signals of sensors, the image obtained from the RTI system is a degraded target image, which cannot offer sufficient details to distinguish different targets. In this paper, we treat the RTI system as an image degraded process, and we propose an estimation model based on mixture Gaussian distribution to derive the degradation function from the shadowing-based RTI model. Then we use this degradation function to recover an original image by a method called constrained least squares filtering. So far, many imaging models have been proposed for localization; however, they do not have a satisfied imaging accuracy. Simulated and experimental results show that the imaging accuracy of our proposed method is improved, and the proposed method can be used in the real-time circumstances.
Small Molecule, Big Prospects: MicroRNA in Pregnancy and Its Complications
Authors: Cai Meng , Kolluru Gopi K. , Ahmed Asif
Published: June 2017

MicroRNAs are small, noncoding RNA molecules that regulate target gene expression in the posttranscriptional level. Unlike siRNA, microRNAs are “fine-tuners” rather than “switches” in the regulation of gene expression; thus they play key roles in maintaining tissue homeostasis. The aberrant microRNA expression is implicated in the disease process. To date, numerous studies have demonstrated the regulatory roles of microRNAs in various pathophysiological conditions. In contrast, the study of microRNA in pregnancy and its associated complications, such as preeclampsia (PE), fetal growth restriction (FGR), and preterm labor, is a young field. Over the last decade, the knowledge of pregnancy-related microRNAs has increased and the molecular mechanisms by which microRNAs regulate pregnancy or its associated complications are emerging. In this review, we focus on the recent advances in the research of pregnancy-related microRNAs, especially their function in pregnancy-associated complications and the potential clinical applications. Here microRNAs that associate with pregnancy are classified as placenta-specific, placenta-associated, placenta-derived circulating, and uterine microRNA according to their localization and origin. MicroRNAs offer a great potential for developing diagnostic and therapeutic targets in pregnancy-related disorders.
The Difference of Neural Networks between Bimanual Antiphase and In-Phase Upper Limb Movements: A Preliminary Functional Magnetic Resonance Imaging Study
Authors: Lin Qiang , Li Hai , Mao Yu-Rong , Lo Wai-Leung , Zhao Jiang-Li , Chen Ling , Leng Yan , Huang Dong-Feng , Li Le
Published: June 2017

Most daily movements require some degree of collaboration between the upper limbs. The neural mechanisms are bimanual-condition specific and therefore should be different between different activities. In this study, we aimed to explore intraregional activation and interregional connectivity during bimanual movement by functional magnetic resonance imaging (fMRI). Ten right-handed, normal subjects were recruited. The neural correlates of unimanual (right side) and bimanual (in-phase and antiphase) upper limb movements were investigated. Connectivity analyses were carried out using the psychophysiological interaction (PPI) model. The cerebellum was strongly activated in both unimanual and bimanual movements, and the cingulate motor area (CMA) was the most activated brain area in antiphase bimanual movement. Moreover, compared with unimanual movement, CMA activation was also observed in antiphase bimanual movement, but not in in-phase bimanual movement. In addition, we carried out the PPI model to study the differences of effective connectivity and found that the cerebellum was more connected with the CMA during antiphase bimanual movement than in-phase bimanual movement. Our findings elucidate the differences of the cerebellar-cerebral functional connectivity between antiphase and in-phase bimanual movements, which could be used to facilitate the development of a neuroscience perspective on bimanual movement control in patients with motor impairments.
SDN-Enabled Communication Network Framework for Energy Internet
Authors: Lu Zhaoming , Sun Chunlei , Cheng Jinqian , Li Yang , Li Yong , Wen Xiangming
Published: June 2017

To support distributed energy generators and improve energy utilization, energy Internet has attracted global research focus. In China, energy Internet has been proposed as an important issue of government and institutes. However, managing a large amount of distributed generators requires smart, low-latency, reliable, and safe networking infrastructure, which cannot be supported by traditional networks in power grids. In order to design and construct smart and flexible energy Internet, we proposed a software defined network framework with both microgrid cluster level and global grid level designed by a hierarchical manner, which will bring flexibility, efficiency, and reliability for power grid networks. Finally, we evaluate and verify the performance of this framework in terms of latency, reliability, and security by both theoretical analysis and real-world experiments.
New Mydriasis-Free Electroretinogram Recorded with Skin Electrodes in Healthy Subjects
Authors: Asakawa Ken , Amino Kana , Iwase Machiho , Kusayanagi Yuki , Nakamura Akiho , Suzuki Rio , Yuuki Takashi , Ishikawa Hitoshi
Published: June 2017

Purpose. To evaluate the reproducibility and consistency of the new mydriasis-free electroretinogram (ERG) with a skin electrode (RETeval) device, to determine the normative values of parameters, and to clarify the usefulness of pupil records to colored-light stimulus.Methods. A total of 100 eyes of 50 healthy subjects (mean age, 21.4 years) were enrolled. The diagnostic parameters obtained by the RETeval device were examined under the following conditions. The reproducibility was determined with the coefficient of variation (CV). The consistency was examined by intraclass correlation coefficients (ICCs). The mean value and the normal range were analyzed with a 95% confidence interval as the normative values of parameters. The correlation of parameters to pupil records (area ratio, constriction ratio) and flicker ERG was also examined in the diabetic retinopathy assessment protocol.Results. From the CV for each of the two measurements, the amplitude has a low reproducibility compared with the implicit time. Generally good consistency was obtained with both ERG parameters (ICCs = 0.48–0.92). Moderate correlations were found for the white-, red-, and blue-light stimulus in the area ratio and the constriction ratio, respectively (r= 0.44–0.62;P= 0.010–<0.0001). No correlation was observed between pupil and flicker parameters (r= 0.06–0.34;P= 0.646–0.051).Conclusions. The RETeval device was suggested as a possible screening device to detect the visual afferent diseases by evaluating in combination with the ERG recording and the colored-light pupil response.
A Pilot Study of Stereotactic Body Radiation Therapy Combined with Cytoreductive Nephrectomy for Metastatic Renal Cell Carcinoma
Authors: Singh Anurag K. , Winslow Timothy B. , Kermany Mohammad Habiby , Goritz Vincent , Heit Lilia , Miller Austin , Hoffend Nicholas C. , Stein Leighton C. , Kumaraswamy Lalith K. , Warren Graham W. , Bshara Wiam , Odunsi Kunle , Matsuzaki Junko , Abrams Scott I. , Schwaab Thomas , Muhitch Jason B.
Published: June 2017

Purpose: While stereotactic body radiotherapy (SBRT) can reduce tumor volumes in patients with metastatic renal cell carcinoma (mRCC), little is known regarding the immunomodulatory effects of high-dose radiation in the tumor microenvironment. The main objectives of this pilot study were to assess the safety and feasibility of nephrectomy following SBRT treatment of patients with mRCC and analyze the immunological impact of high-dose radiation.

Experimental Design: Human RCC cell lines were irradiated and evaluated for immunomodulation. In a single-arm feasibility study, patients with mRCC were treated with 15 Gray SBRT at the primary lesion in a single fraction followed 4 weeks later by cytoreductive nephrectomy. RCC specimens were analyzed for tumor-associated antigen (TAA) expression and T-cell infiltration. The trial has reached accrual (ClinicalTrials.gov identifier: NCT01892930).

Results: RCC cells treated in vitro with radiation had increased TAA expression compared with untreated tumor cells. Fourteen patients received SBRT followed by surgery, and treatment was well-tolerated. SBRT-treated tumors had increased expression of the immunomodulatory molecule calreticulin and TAA (CA9, 5T4, NY-ESO-1, and MUC-1). Ki67+ -proliferating CD8+ T cells and FOXP3+ cells were increased in SBRT-treated patient specimens in tumors and at the tumor–stromal interface compared with archived patient specimens.

Conclusions: It is feasible to perform nephrectomy following SBRT with acceptable toxicity. Following SBRT, patient RCC tumors have increased expression of calreticulin, TAA, as well as a higher percentage of proliferating T cells compared with archived RCC tumors. Collectively, these studies provide evidence of immunomodulation following SBRT in mRCC. Clin Cancer Res; 23(17); 5055–65. ©2017 AACR.
Patient-derived Interstitial Fluids and Predisposition to Aggressive Sporadic Breast Cancer through Collagen Remodeling and Inactivation of p53
Authors: Kenny Timothy C. , Schmidt Hank , Adelson Kerin , Hoshida Yujin , Koh Anna P. , Shah Nagma , Mandeli John , Ting Jess , Germain Doris
Published: June 2017

Purpose: Despite the fact that interstitial fluid (IF) represents a third of our body fluid, it is the most poorly understood body fluid in medicine. Increased IF pressure is thought to result from the increased deposition of extracellular matrix in the affected tissue preventing its reabsorption. In the cancer field, increased rigidity surrounding a cancerous mass remains the main reason that palpation and radiologic examination, such as mammography, are used for cancer detection. While the pressure produced by IF has been considered, the biochemical composition of IF has not been considered in its effect on tumors.

Experimental Design: We classified 135 IF samples from bilateral mastectomy patients based on their ability to promote the invasion of breast cancer cells.

Results: We observed a wide range of invasion scores. Patients with high-grade primary tumors at diagnosis had higher IF invasion scores. In mice, injections of high-score IF (IFHigh) in a normal mammary gland promotes ductal hyperplasia, increased collagen deposition, and local invasion. In a mouse model of residual disease, IFHigh increased disease progression and promoted aggressive visceral metastases. Mechanistically, we found that IFHigh induces myofibroblast differentiation and collagen production through activation of CLIC4. IFHigh also downregulates RYBP, leading to degradation of p53. Furthermore, in mammary glands of heterozygous p53-mutant knock-in mice, IFHigh promotes spontaneous tumor formation.

Conclusions: Our study indicates that IF can increase the deposition of extracellular matrix and raises the provocative possibility that they play an active role in the predisposition, development, and clinical course of sporadic breast cancers. Clin Cancer Res; 23(18); 5446–59. ©2017 AACR.