bluuebunny/crossref_metadata_2025 huggingface dataset:
Magnetic resonance imaging biomarkers of exercise‐induced improvement of oxidative stress and inflammation in the brain of old high‐fat‐fed ApoE−/− mice
Authors: Chirico Erica N. , Di Cataldo Vanessa , Chauveau Fabien , Geloën Alain , Patsouris David , Thézé Benoît , Martin Cyril , Vidal Hubert , Rieusset Jennifer , Pialoux Vincent , Canet‐Soulas Emmanuelle
Published: September 2016

Key points

Vascular brain lesions and atherosclerosis are two similar conditions that are characterized by increased inflammation and oxidative stress.

Non‐invasive imaging in a murine model of atherosclerosis showed vascular brain damage and peripheral inflammation.

In this study, exercise training reduced magnetic resonance imaging‐detected abnormalities, insulin resistance and markers of oxidative stress and inflammation in old ApoE−/− mice.

Our results demonstrate the protective effect of exercise on neurovascular damage in the ageing brain of ApoE−/− mice.

Vascular brain lesions, present in advanced atherosclerosis, share pathological hallmarks with peripheral vascular lesions, such as increased inflammation and oxidative stress. Physical activity reduces these peripheral risk factors, but its cerebrovascular effect is less documented, especially by non‐invasive imaging. Through a combination of in vivo and post‐mortem techniques, we aimed to characterize vascular brain damage in old ApoE−/− mice fed a high‐cholesterol (HC) diet with dietary controlled intake. We then sought to determine the beneficial effects of exercise training on oxidative stress and inflammation in the brain as a treatment option in an ageing atherosclerosis mouse model. Using in vivo magnetic resonance imaging (MRI) and biological markers of oxidative stress and inflammation, we evaluated the occurrence of vascular abnormalities in the brain of HC‐diet fed ApoE−/− mice >70 weeks old, its association with local and systemic oxidative stress and inflammation, and whether both can be modulated by exercise. Exercise training significantly reduced both MRI‐detected abnormalities (present in 71% of untrained vs. 14% of trained mice) and oxidative stress (lipid peroxidation, 9.1 ± 1.4 vs. 5.2 ± 0.9 μmol mg−1; P < 0.01) and inflammation (interleukin‐1β, 226.8 ± 27.1 vs. 182.5 ± 21.5 pg mg−1; P < 0.05) in the brain, and the mortality rate. Exercise also decreased peripheral insulin resistance, oxidative stress and inflammation, but significant associations were seen only within brain markers. Highly localized vascular brain damage is a frequent finding in this ageing atherosclerosis model, and exercise is able to reduce this outcome and improve lifespan. In vivo MRI evaluated both the neurovascular damage and the protective effect of exercise.
On the Hausdorff distance between the shifted Heaviside step function and the transmuted Stannard growth function
Authors: Iliev Anton Iliev , Kyurkchiev Nikolay , Markov Svetoslav
Published: September 2016

In this paper we study the one-sided Hausdorff distance betweenВ the shifted Heaviside step--function and the transmuted Stannard growth function. Precise upper and lower bounds for the Hausdorff distance have been obtained. We present a software module (intellectual property) within the programming environment CAS MathematicaВ for the analysis of the growth curves. Numerical examples, illustrating our results are given, too.
On Capabilities and Limitations of Current Fast Neutron Flux Monitoring Instrumentation for the Demo LFR ALFRED
Authors: Lepore Luigi , Remetti Romolo , Cappelli Mauro
Published: September 2016

Among GEN IV projects for future nuclear power plants, lead-cooled fast reactors (LFRs) seem to be a very interesting solution due to their benefits in terms of fuel cycle, coolant safety, and waste management. The novelty of this matter causes some open issues about coolant chemical aspects, structural aspects, monitoring instrumentation, etc. Particularly, hard neutron flux spectra would make traditional neutron instrumentation unfit to all reactor conditions, i.e., source, intermediate, and power range. Identification of new models of nuclear instrumentation specialized for LFR neutron flux monitoring asks for an accurate evaluation of the environment the sensor will work in. In this study, thermal hydraulics and chemical conditions for the LFR core environment will be assumed, as the neutron flux will be studied extensively by the Monte Carlo transport code MCNPX (Monte Carlo N-Particles X-version). The core coolant’s high temperature drastically reduces the candidate instrumentation because only some kinds of fission chambers and self-powered neutron detectors can be operated in such an environment. This work aims at evaluating the capabilities of the available instrumentation (usually designed and tailored for sodium-cooled fast reactors) when exposed to the neutron spectrum derived from the Advanced Lead Fast Reactor European Demonstrator, a pool-type LFR project to demonstrate the feasibility of this technology into the European framework. This paper shows that such a class of instrumentation does follow the power evolution, but is not completely suitable to detect the whole range of reactor power, due to excessive burnup, damages, or gamma interferences. Some improvements are possible to increase the signal-to-noise ratio by optimizing each instrument in the range of reactor power, so to get the best solution. The design of some new detectors is proposed here together with a possible approach for prototyping and testing them by a fast reactor.
Plastic Collapse Behaviors of Tubulars with Recess Patterns—Application in Hollow Carrier Perforating Guns
Authors: Zhao Haifeng , Iblings David , Barykin Aleksey , Mehdi Mohamed
Published: September 2016

The collapse strength of tubulars with recess patterns machined into their walls is an important topic for oil field downhole tools, especially in hollow carrier perforating gun systems. This paper presents a study of the plastic collapse behavior of thick-walled tubulars (those with an outside diameter to thickness ratio of approximately ten) having different patterns of circular recesses (blind holes partially machined into the tubing wall) that are subjected to external pressure. An empirical relationship between the reduction in collapse strength and the periodic distribution of recesses was constructed to account for the weakening effects of recess diameter, recess depth, axial spacing, angular phasing, etc. This strength reduction factor was introduced into the Tamano formula to predict collapse strength of recessed tubulars. Applicability of this empirical formula was validated with the aid of nonlinear, postbuckling finite element analyses (FEA). The strength reduction factor in combination with the Tamano formula provides a simple way of parametrically predicting the collapse strength of tubulars having circular recess patterns.
Reliability Analysis of Repairable System With Multiple-Input and Multi-Function Component Based on Goal-Oriented Methodology
Authors: Yi Xiao-Jian , Shi Jian , Mu Hui-Na , Dong Hai-Ping , Zhang Zhong
Published: September 2016

This paper proposes a new goal-oriented (GO) method for reliability analysis of repairable systems with multiple-input and multi-function component (MIMFC). First, a new GO operator combination, which is composed of a new function GO operator and a new auxiliary GO operator, is created to represent MIMFC. The new function GO operator named as Type 22 operator is created to represent MIMFC itself, and the auxiliary GO operator named as Type 15B operator is created to represent multi-condition control signals of MIMFC. Then, GO operation formulas of the new GO operator combination are deduced based on logical relationships among inputs, outputs, and the component itself. The reliability analysis process of the new GO method is formulated. Furthermore, this new GO method is applied for the first time in steady availability analysis and qualitative analysis of the fan drive system of a power-shift steering transmission. Finally, the results obtained by the new GO method are compared with the results of fault tree analysis (FTA) and Monte Carlo simulation (MCS), and the comparison results show that this new GO method is reasonable and advantageous in reliability analysis of repairable systems with MIMFC. Moreover, the analysis process shows that it is more advantageous in the aspect of building system models and conducting reliability analysis. Overall, this paper not only improves the basic theory of the GO method and expands the application of the GO method, but it also provides a new approach for reliability analysis of repairable systems with MIMFC.
Assessing the land resource–food price nexus of the Sustainable Development Goals
Authors: Obersteiner Michael , Walsh Brian , Frank Stefan , Havlík Petr , Cantele Matthew , Liu Junguo , Palazzo Amanda , Herrero Mario , Lu Yonglong , Mosnier Aline , Valin Hugo , Riahi Keywan , Kraxner Florian , Fritz Steffen , van Vuuren Detlef
Published: September 2016

Researchers apply an economic model to trade-offs facing the UN’s ambitious Sustainable Development Goals agenda.
Giant electromechanical coupling of relaxor ferroelectrics controlled by polar nanoregion vibrations
Authors: Manley Michael E. , Abernathy Douglas L. , Sahul Raffi , Parshall Daniel E. , Lynn Jeffrey W. , Christianson Andrew D. , Stonaha Paul J. , Specht Eliot D. , Budai John D.
Published: September 2016

Polar nanoregion vibrations control the ultrahigh piezoelectric response of relaxor-based ferroelectrics used in applications.
Cyclic di-GMP mediates a histidine kinase/phosphatase switch by noncovalent domain cross-linking
Authors: Dubey Badri N. , Lori Christian , Ozaki Shogo , Fucile Geoffrey , Plaza-Menacho Ivan , Jenal Urs , Schirmer Tilman
Published: September 2016

Multidisciplinary study reveals the mechanism for second messenger–mediated regulation of a central bacterial cell cycle kinase.
Anthropocene rockfalls travel farther than prehistoric predecessors
Authors: Borella Josh Walter , Quigley Mark , Vick Louise
Published: September 2016

Anthropogenic deforestation increases rockfall hazard in southern Christchurch, New Zealand.
Selection of Amine-Oxidizing Dairy Lactic Acid Bacteria and Identification of the Enzyme and Gene Involved in the Decrease of Biogenic Amines
Authors: Guarcello Rosa , De Angelis Maria , Settanni Luca , Formiglio Sabino , Gaglio Raimondo , Minervini Fabio , Moschetti Giancarlo , Gobbetti Marco
Published: September 2016

Accumulation of biogenic amines (BAs) in cheese and other foods is a matter of public health concern. The aim of this study was to identify the enzyme activities responsible for BA degradation in lactic acid bacteria which were previously isolated from traditional Sicilian and Apulian cheeses. The selected strains would control the concentration of BAs during cheese manufacture. First, 431 isolates not showing genes encoding the decarboxylases responsible for BA formation were selected using PCR-based methods. Ninety-four out of the 431 isolates degraded BAs (2-phenylethylamine, cadaverine, histamine, putrescine, spermine, spermidine, tyramine, or tryptamine) during cultivation on chemically defined medium. As shown by random amplification of polymorphic DNA-PCR and partial sequencing of the 16S rRNA gene, 78 of the 94 strains were
Lactobacillus
species (
Lactobacillus casei
,
Lb. fermentum
,
Lb. parabuchneri
,
Lb. paracasei
,
Lb. paraplantarum
, and
Lb. rhamnosus
),
Leuconostoc
species (
Leuconostoc lactis
and
Ln. mesenteroides
),
Pediococcus pentosaceus
,
Lactococcus lactis
,
Streptococcus
species (
Streptococcus
gallolyticus
and
S. thermophilus
),
Enterococcus lactis
, and
Weissella paramesenteroides
. A multicopper oxidase-hydrolyzing BA was purified from the most active strain,
Lb. paracasei
subsp.
paracasei
CB9CT. The gene encoding the multicopper oxidase was sequenced and was also detected in other amine-degrading strains of
Lb. fermentum
,
Lb. paraplantarum
, and
P. pentosaceus
.
Lb. paracasei
subsp.
paracasei
CB9CT and another strain (CACIO6CT) of the same species that was able to degrade all the BAs were singly used as adjunct starters for decreasing the concentration of histamine and tyramine in industrial Caciocavallo cheese. The results of this study disclose a feasible strategy for increasing the safety of traditional cheeses while maintaining their typical sensorial traits.

IMPORTANCE
Because high concentrations of the potentially toxic biogenic amines may be found in traditional/typical cheeses, the safety of these food items should be improved. Lactic acid bacteria selected for the ability to degrade biogenic amines may be used during cheese making to control the concentrations of biogenic amines.
In Vivo
Analysis of NH
4
+
Transport and Central Nitrogen Metabolism in Saccharomyces cerevisiae during Aerobic Nitrogen-Limited Growth
Authors: Cueto-Rojas H. F. , Maleki Seifar R. , ten Pierick A. , van Helmond W. , Pieterse M. M. , Heijnen J. J. , Wahl S. A.
Published: September 2016

Ammonium is the most common N source for yeast fermentations. Although its transport and assimilation mechanisms are well documented, there have been only a few attempts to measure the
in vivo
intracellular concentration of ammonium and assess its impact on gene expression. Using an isotope dilution mass spectrometry (IDMS)-based method, we were able to measure the intracellular ammonium concentration in N-limited aerobic chemostat cultivations using three different N sources (ammonium, urea, and glutamate) at the same growth rate (0.05 h
−1
). The experimental results suggest that, at this growth rate, a similar concentration of intracellular (IC) ammonium, about 3.6 mmol NH
4
+
/liter
IC
, is required to supply the reactions in the central N metabolism, independent of the N source. Based on the experimental results and different assumptions, the vacuolar and cytosolic ammonium concentrations were estimated. Furthermore, we identified a futile cycle caused by NH
3
leakage into the extracellular space, which can cost up to 30% of the ATP production of the cell under N-limited conditions, and a futile redox cycle between Gdh1 and Gdh2 reactions. Finally, using shotgun proteomics with protein expression determined relative to a labeled reference, differences between the various environmental conditions were identified and correlated with previously identified N compound-sensing mechanisms.

IMPORTANCE
In our work, we studied central N metabolism using quantitative approaches. First, intracellular ammonium was measured under different N sources. The results suggest that
Saccharomyces cerevisiae
cells maintain a constant NH
4
+
concentration (around 3 mmol NH
4
+
/liter
IC
), independent of the applied nitrogen source. We hypothesize that this amount of intracellular ammonium is required to obtain sufficient thermodynamic driving force. Furthermore, our calculations based on thermodynamic analysis of the transport mechanisms of ammonium suggest that ammonium is not equally distributed, indicating a high degree of compartmentalization in the vacuole. Additionally, metabolomic analysis results were used to calculate the thermodynamic driving forces in the central N metabolism reactions, revealing that the main reactions in the central N metabolism are far from equilibrium. Using proteomics approaches, we were able to identify major changes, not only in N metabolism, but also in C metabolism and regulation.
Peeking under the Iron Curtain: Development of a Microcosm for Imaging the Colonization of Steel Surfaces by Mariprofundus sp. Strain DIS-1, an Oxygen-Tolerant Fe-Oxidizing Bacterium
Authors: Mumford Adam C. , Adaktylou Irini J. , Emerson David
Published: September 2016

Microbially influenced corrosion (MIC) is a major cause of damage to steel infrastructure in the marine environment. Despite their ability to grow directly on Fe(II) released from steel, comparatively little is known about the role played by neutrophilic iron-oxidizing bacteria (FeOB). Recent work has shown that FeOB grow readily on mild steel (1018 MS) incubated
in situ
or as a substrate for pure cultures
in vitro
; however, details of how they colonize steel surfaces are unknown yet are important for understanding their effects. In this study, we combine a novel continuously upwelling microcosm with confocal laser scanning microscopy (CLSM) to determine the degree of colonization of 1018 MS by the marine FeOB strain DIS-1. 1018 MS coupons were incubated with sterile seawater (pH 8) inoculated with strain DIS-1. Incubations were performed both under oxic conditions and in an anoxic-to-oxic gradient. Following incubations of 1 to 10 days, the slides were removed from the microcosms and stained to visualize both cells and stalk structures. Stained coupons were visualized by CLSM after being mounted in a custom frame to preserve the three-dimensional structure of the biofilm. The incubation of 1018 MS coupons with strain DIS-1 under oxic conditions resulted in initial attachment of cells within 2 days and nearly total coverage of the coupon with an ochre film within 5 days. CLSM imaging revealed a nonadherent biofilm composed primarily of the Fe-oxide stalks characteristic of strain DIS-1. When incubated with elevated concentrations of Fe(II), DIS-1 colonization of 1018 MS was inhibited.

IMPORTANCE
These experiments describe the growth of a marine FeOB in a continuous culture system and represent direct visualizations of steel colonization by FeOB. We anticipate that these experiments will lay the groundwork for studying the mechanisms by which FeOB colonize steel and help to elucidate the role played by marine FeOB in MIC. These observations of the interaction between an FeOB, strain DIS-1, and steel suggest that this experimental system will provide a useful model for studying the interactions between microbes and solid substrates.
Metabolism of Fructophilic Lactic Acid Bacteria Isolated from the Apis mellifera L. Bee Gut: Phenolic Acids as External Electron Acceptors
Authors: Filannino Pasquale , Di Cagno Raffaella , Addante Rocco , Pontonio Erica , Gobbetti Marco
Published: September 2016

Fructophilic lactic acid bacteria (FLAB) are strongly associated with the gastrointestinal tracts (GITs) of
Apis mellifera
L. worker bees due to the consumption of fructose as a major carbohydrate. Seventy-seven presumptive lactic acid bacteria (LAB) were isolated from GITs of healthy
A. mellifera
L. adults, which were collected from 5 different geographical locations of the Apulia region of Italy. Almost all of the isolates showed fructophilic tendencies: these isolates were identified as
Lactobacillus kunkeei
(69%) or
Fructobacillus fructosus
(31%). A high-throughput phenotypic microarray targeting 190 carbon sources was used to determine that 83 compounds were differentially consumed. Phenotyping grouped the strains into two clusters, reflecting growth performance. The utilization of phenolic acids, such as
p
-coumaric, caffeic, syringic, or gallic acids, as electron acceptors was investigated in fructose-based medium. Almost all FLAB strains showed tolerance to high phenolic acid concentrations.
p
-Coumaric acid and caffeic acid were consumed by all FLAB strains through reductases or decarboxylases. Syringic and gallic acids were partially metabolized. The data collected suggest that FLAB require external electron acceptors to regenerate NADH. The use of phenolic acids as external electron acceptors by the 4 FLAB showing the highest phenolic acid reductase activity was investigated in glucose-based medium supplemented with
p
-coumaric acid. Metabolic responses observed through a phenotypic microarray suggested that FLAB may use
p
-coumaric acid as an external electron acceptor, enhancing glucose dissimilation but less efficiently than other external acceptors such as fructose or pyruvic acid.

IMPORTANCE
Fructophilic lactic acid bacteria (FLAB) remain to be fully explored. This study intends to link unique biochemical features of FLAB with their habitat. The quite unique FLAB phenome within the group lactic acid bacteria (LAB) may have practical relevance in food fermentations. The FLAB phenome may have implications for the levels of hexose metabolism products in fermented foods, as well as food probiotication. Due to the harsh conditions of honeybees' GITs, these bacteria had to develop specific physiological and biochemical characteristics, such as tolerance to phenolic acids. The screening of FLAB strains based on metabolic pathways involving phenolic acids may allow the selection of starter cultures with both technological and functional beneficial attributes. Bioconversion of phenolic compounds may contribute to the aroma attributes and biofunctionality of fermented foods. Thus, the selection of FLAB strains as starter cultures with specific enzymatic activities involving phenolic acids may have a promising role in food fermentations.
Microbial Herd Protection Mediated by Antagonistic Interaction in Polymicrobial Communities
Authors: Wong Megan J. Q. , Liang Xiaoye , Smart Matt , Tang Le , Moore Richard , Ingalls Brian , Dong Tao G.
Published: September 2016

In host and natural environments, microbes often exist in complex multispecies communities. The molecular mechanisms through which such communities develop and persist, despite significant antagonistic interactions between species, are not well understood. The type VI secretion system (T6SS) is a lethal weapon commonly employed by Gram-negative bacteria to inhibit neighboring species through the delivery of toxic effectors. It is well established that intraspecies protection is conferred by immunity proteins that neutralize effector toxicities. In contrast, the mechanisms for interspecies protection are not clear. Here we use two T6SS-active antagonistic bacterial species,
Aeromonas hydrophila
and
Vibrio cholerae
, to demonstrate that interspecies protection is dependent on effectors.
A. hydrophila
and
V. cholerae
do not share conserved immunity genes but could coexist equally in a mixture. However, mutants lacking the T6SS or effectors were effectively eliminated by the competing wild-type strain. Time-lapse microscopic analyses showed that mutually lethal interactions drive the segregation of mixed species into distinct single-species clusters by eliminating interspersed single cells. Cluster formation provides herd protection by abolishing lethal interactions inside each cluster and restricting the interactions to the boundary. Using an agent-based modeling approach, we simulated the antagonistic interactions of two hypothetical species. The resulting simulations recapitulated our experimental observations. These results provide mechanistic insights regarding the general role of microbial weapons in determining the structures of complex multispecies communities.

IMPORTANCE
Investigating the warfare of microbes allows us to better understand the ecological relationships in complex microbial communities such as the human microbiota. Here we use the T6SS, a deadly bacterial weapon, as a model to demonstrate the importance of lethal interactions in determining community structures and the exchange of genetic materials. This simplified model elucidates a mechanism of microbial herd protection by which competing antagonistic species can coexist in the same niche, despite their diverse mutually destructive activities. Our results also suggest that antagonistic interactions impose strong selection that could promote multicellular organism-like social behaviors and contribute to the transition to multicellularity during evolution.
Generation of a Stable Plasmid for
In Vitro
and
In Vivo
Studies of Staphylococcus Species
Authors: Krute Christina N. , Krausz Kelsey L. , Markiewicz Mary A. , Joyner Jason A. , Pokhrel Srijana , Hall Pamela R. , Bose Jeffrey L.
Published: September 2016

A major shortcoming to plasmid-based genetic tools is the necessity of using antibiotics to ensure plasmid maintenance. While selectable markers are very powerful, their use is not always practical, such as during
in vivo
models of bacterial infection. During previous studies, it was noted that the uncharacterized LAC-p01 plasmid in
Staphylococcus aureus
USA300 isolates was stable in the absence of a known selection and therefore could serve as a platform for new genetic tools for
Staphylococcus
species. LAC-p01 was genetically manipulated into an
Escherichia coli
-
S. aureus
shuttle vector that remained stable for at least 100 generations without antibiotic selection. The double- and single-stranded (
dso
and
sso
) origins were identified and found to be essential for plasmid replication and maintenance, respectively. In contrast, deletion analyses revealed that none of the four LAC-p01 predicted open reading frames were necessary for stability. Subsequent to this, the shuttle vector was used as a platform to generate two plasmids. The first plasmid, pKK22, contains all genes native to the plasmid for use in
S. aureus
USA300 strains, while the second, pKK30, lacks the four predicted open reading frames for use in non-USA300 isolates. pKK30 was also determined to be stable in
Staphylococcus epidermidis
. Moreover, pKK22 was maintained for 7 days postinoculation during a murine model of
S. aureus
systemic infection and successfully complemented an
hla
mutant in a dermonecrosis model. These plasmids that eliminate the need for antibiotics during both
in vitro
and
in vivo
experiments are powerful new tools for studies of
Staphylococcus
.

IMPORTANCE
Plasmid stability has been problematic in bacterial studies, and historically antibiotics have been used to ensure plasmid maintenance. This has been a major limitation during
in vivo
studies, where providing antibiotics for plasmid maintenance is difficult and has confounding effects. Here, we have utilized the naturally occurring plasmid LAC-p01 from an
S. aureus
USA300 strain to construct stable plasmids that obviate antibiotic usage. These newly modified plasmids retain stability over a multitude of generations
in vitro
and
in vivo
without antibiotic selection. With these plasmids, studies requiring genetic complementation, protein expression, or genetic reporter systems would not only overcome the burden of antibiotic usage but also eliminate the side effects of these antibiotics. Thus, our plasmids can be used as a powerful genetic tool for studies of
Staphylococcus
species.
The Redox Cofactor F
420
Protects Mycobacteria from Diverse Antimicrobial Compounds and Mediates a Reductive Detoxification System
Authors: Jirapanjawat Thanavit , Ney Blair , Taylor Matthew C. , Warden Andrew C. , Afroze Shahana , Russell Robyn J. , Lee Brendon M. , Jackson Colin J. , Oakeshott John G. , Pandey Gunjan , Greening Chris
Published: September 2016

A defining feature of mycobacterial redox metabolism is the use of an unusual deazaflavin cofactor, F
420
. This cofactor enhances the persistence of environmental and pathogenic mycobacteria, including after antimicrobial treatment, although the molecular basis for this remains to be understood. In this work, we explored our hypothesis that F
420
enhances persistence by serving as a cofactor in antimicrobial-detoxifying enzymes. To test this, we performed a series of phenotypic, biochemical, and analytical chemistry studies in relation to the model soil bacterium
Mycobacterium smegmatis
. Mutant strains unable to synthesize or reduce F
420
were found to be more susceptible to a wide range of antibiotic and xenobiotic compounds. Compounds from three classes of antimicrobial compounds traditionally resisted by mycobacteria inhibited the growth of F
420
mutant strains at subnanomolar concentrations, namely, furanocoumarins (e.g., methoxsalen), arylmethanes (e.g., malachite green), and quinone analogues (e.g., menadione). We demonstrated that promiscuous F
420
H
2
-dependent reductases directly reduce these compounds by a mechanism consistent with hydride transfer. Moreover,
M. smegmatis
strains unable to make F
420
H
2
lost the capacity to reduce and detoxify representatives of the furanocoumarin and arylmethane compound classes in whole-cell assays. In contrast, mutant strains were only slightly more susceptible to clinical antimycobacterials, and this appeared to be due to indirect effects of F
420
loss of function (e.g., redox imbalance) rather than loss of a detoxification system. Together, these data show that F
420
enhances antimicrobial resistance in mycobacteria and suggest that one function of the F
420
H
2
-dependent reductases is to broaden the range of natural products that mycobacteria and possibly other environmental actinobacteria can reductively detoxify.

IMPORTANCE
This study reveals that a unique microbial cofactor, F
420
, is critical for antimicrobial resistance in the environmental actinobacterium
Mycobacterium smegmatis
. We show that a superfamily of redox enzymes, the F
420
H
2
-dependent reductases, can reduce diverse antimicrobials
in vitro
and
in vivo
.
M. smegmatis
strains unable to make or reduce F
420
become sensitive to inhibition by these antimicrobial compounds. This suggests that mycobacteria have harnessed the unique properties of F
420
to reduce structurally diverse antimicrobials as part of the antibiotic arms race. The F
420
H
2
-dependent reductases that facilitate this process represent a new class of antimicrobial-detoxifying enzymes with potential applications in bioremediation and biocatalysis.
Developmental trajectories in children with prolonged NICU stays
Authors: Subedi Dibya , DeBoer Mark D , Scharf Rebecca J
Published: September 2016

Objective

To evaluate the relationship between prolonged neonatal intensive care unit (NICU) stay after birth and childhood neurodevelopmental measures from age 9 months to kindergarten.

Design

Longitudinal birth cohort study.

Setting and patients

This study examined a nationally representative sample of 10 700 participants from the Early Childhood Longitudinal Sample—Birth Cohort and selected those who had a NICU stay (n=2100). These children were followed from birth to kindergarten.

Predictors

Days in the NICU.

Main outcome measures

Childhood neurodevelopmental and early academic scores.

Results

Increasing length of stay in the NICU had a significant negative relationship with the 9-month and 24-month Bayley mental and motor scores. Each additional week in the NICU increased the odds of scoring in the lowest 10% on the Bayley 9-month mental (OR 1.08, 95% CI 1.034 to 1.122) and motor (OR 1.11, CI 1.065 to 1.165) assessments and 24-month mental (OR 1.09, CI 1.041 to 1.144) and motor assessments (OR 1.07 CI 1.017 to 1.123). Gestational age was not significantly related with these measures in our model. Increasing socioeconomic status had a significant positive relationship with preschool and kindergarten reading and math scores and a lower odds of scoring in the lowest 10% in these measures.

Conclusion

Increasing length of NICU stay was predictive of decreased child development measures in early childhood (9 and 24 months), while socioeconomic status was a better predictor at later assessments (preschool and kindergarten entries). Gestational category did not account for these differences. These data may have implications for counselling parents regarding potential neurodevelopmental consequences following NICU stay.
Gastric microbiota in the functional dyspepsia patients treated with probiotic yogurt
Authors: Nakae Hirohiko , Tsuda Ayumi , Matsuoka Takashi , Mine Tetsuya , Koga Yasuhiro
Published: September 2016

Objective

To investigate the structure of the gastric microbiota in functional dyspepsia (FD) and its role in the pathophysiology.

Design

We compared the basic physiological properties of the gastric fluid (GF) and the structure of the microbiota in the GF of 44 healthy control (HC) participants and 44 patients with FD. We then treated the patients with FD with a yogurt containing a probiotic strain ofLactobacillus gasseriOLL2716 (LG21 yogurt) and investigated the effects on the bacteriological parameters and symptoms to examine the relationship between them.

Results

The volume of GF recovered from the stomach after overnight fasting was greater in the patients with FD than in the HCs, and decreased in the patients with FD whose symptoms were improved by the LG21 yogurt treatment. An analysis using a terminal restriction fragment polymorphism method demonstrated that the overall structure of the bacterial community and the abundance of genusPrevotellain the GF of the patients in the FD group were significantly different from those in the HC group. In the patients with FD, this bacteriological change was restored by treatment with LG21 yogurt. A significant inverse correlation was found between the abundance ofPrevotellaand the severity of postprandial distress-like symptoms in patients with FD who received LG21 yogurt.

Conclusions

Significant dysbiosis was found in the GF microbiota of patients with FD and considered to be involved in the pathogenesis. The abundance of genusPrevotellain the GF may be used as a biomarker of the efficacy of the treatment of FD.

Trial registration number

UMINCTR000022026.
Barriers to making recommendations about medical tests: a qualitative study of European guideline developers
Authors: Gopalakrishna Gowri , Leeflang Mariska M G , Davenport Clare , Sanabria Andrea Juliana , Alonso-Coello Pablo , McCaffery Kirsten , Bossuyt Patrick , Langendam Miranda W
Published: September 2016

Objectives

Development of medical test guidelines differs from intervention guideline development. These differences can pose unique challenges in building evidence-based recommendations to guide clinical practice. The aim of our study was to better understand these challenges, explore reasons behind them and identify possible solutions.

Setting and participants

In this qualitative study, we conducted in-depth interviews between February 2012 and April 2013 of a convenience sample of 17 European guideline developers experienced in medical test guideline development.

Outcomes measured

We used framework analysis with deductive and inductive approaches to generate the themes from the interviews. We kept interpretation grounded in the data.

Results

Guideline developers acknowledged that inclusion of patient important outcomes in their guideline development was necessary but lacking. This and other challenges raised fell into 3 broad and overlapping domains: methodological issues, resource limitations and a lack of awareness on the need for evidence that links testing to patient outcomes. Education was mentioned as a key solution to increase awareness and address the resources limitations mentioned.

Conclusions

Challenges guideline developers face were interlinked across the domains of methodological issues, resource limitations and a lack of awareness. Solutions that addressed these challenges in parallel are needed. Raising awareness, education and training of relevant stakeholders such as medical doctors, funders and regulators to look beyond test accuracy is key to having a long-term resolution to the issues faced in medical test guideline development.
Scientific research output in orthopaedics from China and other top-ranking countries: a 10-year survey of the literature
Authors: Zou Yuming , Li Quan , Xu Weidong
Published: September 2016

Objectives

Orthopaedics-related diseases and conditions are a significant burden worldwide. In this study, we aimed to compare the quantity and quality of research output in the field of orthopaedics from Mainland China (MC), USA, UK, Japan and Germany.

Setting

The USA, UK, Japan, Germany and MC.

Participants

We selected orthopaedics journals from the subject category ‘orthopedics’ from the Science Citation Index Expanded (SCIE).

Outcome measures

The number of publications, the number of publications in the surveyed publication types, impact factor (IF) and citations from the corresponding country from 2005 to 2014 were collected for quantity and quality comparisons.

Results

A total of 128 895 articles were published worldwide in orthopaedics-related journals from 2005 to 2014. The USA contributed the largest proportion (31 190 (24.20%)), followed by the UK (6703 (5.20%)), Japan (5718 (4.41%)), Germany (4701 (3.66%)) and MC (3389 (2.63%)). Publications from MC represented the fewest, but this quantity is rapidly increasing. The quantity of annual publications from MC has exceeded that of Germany since 2012. The USA plays a predominant role in all kinds of publication types under investigation in the study, except in the category of meta-analysis. MC was in the last place for cumulative IFs, and the average IF actually decreased from the beginning of the study. For total and average citations, MC still lags behind the other countries in the study.

Conclusions

The USA has occupied the dominant place in orthopaedics-related research for the last 10 years. Although MC has made great progress in the number of published works in the field of orthopaedics over the last 10 years, the quality of these publishing efforts needs further improvement.
Dual-process cognitive interventions to enhance diagnostic reasoning: a systematic review
Authors: Lambe Kathryn Ann , O'Reilly Gary , Kelly Brendan D , Curristan Sarah
Published: September 2016

Background

Diagnostic error incurs enormous human and economic costs. The dual-process model reasoning provides a framework for understanding the diagnostic process and attributes certain errors to faulty cognitive shortcuts (heuristics). The literature contains many suggestions to counteract these and to enhance analytical and non-analytical modes of reasoning.

Aims

To identify, describe and appraise studies that have empirically investigated interventions to enhance analytical and non-analytical reasoning among medical trainees and doctors, and to assess their effectiveness.

Methods

Systematic searches of five databases were carried out (Medline, PsycInfo, Embase, Education Resource Information Centre (ERIC) and Cochrane Database of Controlled Trials), supplemented with searches of bibliographies and relevant journals. Included studies evaluated an intervention to enhance analytical and/or non-analytical reasoning among medical trainees or doctors.

Findings

Twenty-eight studies were included under five categories: educational interventions, checklists, cognitive forcing strategies, guided reflection, instructions at test and other interventions. While many of the studies found some effect of interventions, guided reflection interventions emerged as the most consistently successful across five studies, and cognitive forcing strategies improved accuracy and confidence judgements. Significant heterogeneity of measurement approaches was observed, and existing studies are largely limited to early-career doctors.

Conclusions

Results to date are promising and this relatively young field is now close to a point where these kinds of cognitive interventions can be recommended to educators. Further research with refined methodology and more diverse samples is required before firm recommendations may be made for medical education and policy; however, these results suggest that such interventions hold promise, with much current enthusiasm for new research.
Axially symmetric holographic dark energy model with generalized Chaplygin gas in Brans–Dicke theory of gravitation
Authors: Rao V.U.M. , Sireesha K.V.S.
Published: September 2016

In this paper, spatially homogeneous anisotropic axially symmetric holographic dark energy cosmological model with generalized Chaplygin gas is obtained in a scalar–tensor theory of gravitation proposed by Brans and Dicke (Phys. Rev. 124, 925 (1961)). To obtain a determinate solution of the field equations we have used a power law between the metric potentials. It has been found that the anisotropic distribution of dark energy leads to the present accelerated expansion of the Universe. All the models obtained and presented here are expanding, non-rotating, and accelerating. Also some important features of the models including look-back time, distance modulus, and luminosity distance versus redshift, and their significances are discussed.
Relations between entanglement and purity in non-Markovian dynamics
Authors: González-Gutiérrez Carlos A. , Román-Ancheyta Ricardo , Espitia Diego , Lo Franco Rosario
Published: September 2016

Knowledge of the relationships among different features of quantumness, like entanglement and state purity, is important from both fundamental and practical viewpoints. Yet, this issue remains little explored in dynamical contexts for open quantum systems. We address this problem by studying the dynamics of entanglement and purity for two-qubit systems using paradigmatic models of radiation-matter interaction, with a qubit being isolated from the environment (spectator configuration). We show the effects of the corresponding local quantum channels on an initial two-qubit pure entangled state in the concurrence–purity diagram and find the conditions which enable dynamical closed formulas of concurrence, used to quantify entanglement, as a function of purity. We finally discuss the usefulness of these relations in assessing entanglement and purity thresholds which allow noisy quantum teleportation. Our results provide new insights about how different properties of composite open quantum systems behave and relate each other during quantum evolutions.
Structural style in a Messinian (intra-Pontian) gravity-driven deformation system, western Black Sea, offshore Romania
Authors: Schleder Z. , Krezsek C. , Lapadat A. , Bega Z. , Ionescu G. , Tari G.
Published: September 2016

Miocene sediments of the western Black Sea failed gravitationally during the intra-Pontian (Messinian) sea-level fall. In the region of the Histria Trough, this generated two independent collapse systems detaching on the upper part of Oligocene–Lower Miocene shale. This contribution focuses on the eastern system. The eastern linked system is approximately 60 km long in the dip direction, containing about 10 major extensional faults in the updip domain, with a cumulative extension (heave) of 11.4 km. This extension is accommodated downdip partially by 6 – 7 km of lateral compaction and on a single toe thrust with 4.8 km of shortening.

The thin-skinned extension generated both basinwards-dipping faults and counter-regional faults (dip towards the basin margin), with associated rollovers, tilted fault blocks and keystone graben. Broad shale pillow (3 km across) and cuspate shale upwelling developed due to reactive shale diapirism. The collapse of the rollover anticlines into the half-graben suggests a high deformation rate. Downdip, the thrust follows the top of the Oligocene–Lower Miocene unit and steps up into the top of Sarmatian. The thrust hanging-wall anticline collapsed and triggered a mass transport complex (MTC). The top of the MTC is a rugose surface, and we suggest that it remained under water during the Messinian event due to its lack of visible erosion.
Gravity-driven deformation of a youthful saline giant: the interplay between gliding and spreading in the Messinian basins of the Eastern Mediterranean
Authors: Allen Hayley , Jackson Christopher A.-L. , Fraser Alastair J.
Published: September 2016

The triggers and drivers for salt-related deformation on continental margins are intensely debated, reflecting uncertainties regarding the diagnostic value of certain structural styles, in addition to the fundamental mechanics associated with the two principal mechanisms (gliding and spreading). Determining the triggers and drivers for salt-related deformation is important because they provide insights into continent-scale geodynamic processes, the regional kinematics of gravity-driven deformation, and sediment dispersal and hydrocarbon prospectivity. The processes associated with and the timing of deformation of Messinian salt in the offshore Eastern Mediterranean are uncertain, and thus so is our understanding of the geodynamic evolution of this tectonically complex region. We here use an extensive 2D and 3D seismic reflection dataset to test models for the salt-tectonic development of Messinian salt. We contend that gliding and spreading were not mutually exclusive, but were likely to have overlapped in time and space, being associated with local and far-field tectonics (gliding), as well as differential overburden loading (spreading). We also argue that intrasalt strain and seismic-stratigraphic patterns can be explained by a model invoking a single, post-Messinian period of salt-related deformation, rather than a more complex model involving two separate deformation events that occurred during and after salt deposition.
Middle Pleistocene glaciation, alluvial fan development and sea-level changes in the Bay of Kotor, Montenegro
Authors: Adamson K. R. , Woodward J. C. , Hughes P. D. , Giglio F. , Del Bianco F.
Published: September 2016

A coarse-grained alluvial fan at Lipci in the Bay of Kotor, western Montenegro, was deposited in the Middle Pleistocene by a high-energy, steep gradient proglacial stream draining an outlet glacier on the Orjen massif. The fan apex is currently about 50 m above sea-level, but the majority (
c.
60%) of this landform now lies offshore. Field mapping, sedimentological analysis and uranium-series dating were combined with a marine bathymetric survey and seismic profiling to explore the morphology and history of the entire fan complex. The Lipci fan was deposited on the margin of a large polje downstream of moraines that formed during the Middle Pleistocene (Marine Isotope Stage 12). The sea-level may have been more than 120 m lower than present during the glacial stages of the Middle Pleistocene. The sediments on the terrestrial portion of the fan are strongly cemented by secondary calcite and the oldest uranium-series ages show that the fan was deposited before 320 ka. These ages are consistent with a larger uranium-series dataset (
n
=39) from other glacial and glacio-fluvial formations surrounding Mount Orjen. Seismic profiling of the submerged portion of the fan in the Bay of Kotor shows well-preserved palaeochannels with inset terraces. The Lipci fan is unusual because even its distal segments are well preserved after exposure to multiple post-Marine Isotope Stage 12 regression–transgression cycles. This is probably due to the strong cementation of the fan sediments and its sheltered location in the Bay of Kotor.
Understanding GPU Power
Authors: Bridges Robert A. , Imam Neena , Mintz Tiffany M.
Published: September 2016

Modern graphics processing units (GPUs) have complex architectures that admit exceptional performance and energy efficiency for high-throughput applications. Although GPUs consume large amounts of power, their use for high-throughput applications facilitate state-of-the-art energy efficiency and performance. Consequently, continued development relies on understanding their power consumption. This work is a survey of GPU power modeling and profiling methods with increased detail on noteworthy efforts. As direct measurement of GPU power is necessary for model evaluation and parameter initiation, internal and external power sensors are discussed. Hardware counters, which are low-level tallies of hardware events, share strong correlation to power use and performance. Statistical correlation between power and performance counters has yielded worthwhile GPU power models, yet the complexity inherent to GPU architectures presents new hurdles for power modeling. Developments and challenges of counter-based GPU power modeling are discussed. Often building on the counter-based models, research efforts for GPU power simulation, which make power predictions from input code and hardware knowledge, provide opportunities for optimization in programming or architectural design. Noteworthy strides in power simulations for GPUs are included along with their performance or functional simulator counterparts when appropriate. Last, possible directions for future research are discussed.