bluuebunny/crossref_metadata_2025 huggingface dataset:
Colistin Is Extensively Lost during Standard
In Vitro
Experimental Conditions
Authors: Karvanen Matti , Malmberg Christer , Lagerbäck Pernilla , Friberg Lena E. , Cars Otto
Published: September 2017

Colistin adheres to a range of materials, including plastics in labware. The loss caused by adhesion influences an array of methods detrimentally, including MIC assays and
in vitro
time-kill experiments. The aim of this study was to characterize the extent and time course of colistin loss in different types of laboratory materials during a simulated time-kill experiment without bacteria or plasma proteins present. Three types of commonly used large test tubes, i.e., soda-lime glass, polypropylene, and polystyrene, were studied, as well as two different polystyrene microplates and low-protein-binding microtubes. The tested concentration range was 0.125 to 8 mg/liter colistin base. Exponential one-phase and two-phase functions were fitted to the data, and the adsorption of colistin to the materials was modeled with the Langmuir adsorption model. In the large test tubes, the measured start concentrations ranged between 44 and 102% of the expected values, and after 24 h, the concentrations ranged between 8 and 90%. The half-lives of colistin loss were 0.9 to 12 h. The maximum binding capacities of the three materials ranged between 0.4 and 1.1 μg/cm
2
, and the equilibrium constants ranged between 0.10 and 0.54 ml/μg. The low-protein-binding microtubes showed start concentrations between 63 and 99% and concentrations at 24 h of between 59 and 90%. In one of the microplates, the start concentrations were below the lower limit of quantification at worst. In conclusion, to minimize the effect of colistin loss due to adsorption, our study indicates that low-protein-binding polypropylene should be used when possible for measuring colistin concentrations in experimental settings, and the results discourage the use of polystyrene. Furthermore, when diluting colistin in protein-free media, the number of dilution steps should be minimized.
Inactivation of Human Norovirus Genogroups I and II and Surrogates by Free Chlorine in Postharvest Leafy Green Wash Water
Authors: Dunkin Nathan , Weng ShihChi , Jacangelo Joseph G. , Schwab Kellogg J.
Published: September 2017

Human noroviruses (hNoVs) are a known public health concern associated with the consumption of leafy green vegetables. While a number of studies have investigated pathogen reduction on the surfaces of leafy greens during the postharvest washing process, there remains a paucity of data on the level of treatment needed to inactivate viruses in the wash water, which is critical for preventing cross-contamination. The objective of this study was to quantify the susceptibility of hNoV genotype I (GI), hNoV GII, murine norovirus (MNV), and bacteriophage MS2 to free chlorine in whole leaf, chopped romaine, and shredded iceberg lettuce industrial leafy green wash waters, each sampled three times over a 4-month period. A suite of kinetic inactivation models was fit to the viral reduction data to aid in quantification of concentration-time (CT) values. Results indicate that 3-log
10
infectivity reduction was achieved at CT values of less than 0.2 mg · min/liter for MNV and 2.5 mg · min/liter for MS2 in all wash water types. CT values for 2-log
10
molecular reduction of hNoV GI in whole leaf and chopped romaine wash waters were 1.5 and 0.9 mg · min/liter, respectively. For hNoV GII, CT values were 13.0 and 7.5 mg · min/liter, respectively. In shredded iceberg wash water, 3-log
10
molecular reduction was not observed for any virus over the time course of experiments. These findings demonstrate that noroviruses may exhibit genogroup-dependent resistance to free chlorine and emphasize the importance of distinguishing between genogroups in hNoV persistence studies.

IMPORTANCE
Postharvest washing of millions of pounds of leafy greens is performed daily in industrial processing facilities with the intention of removing dirt, debris, and pathogenic microorganisms prior to packaging. Modest inactivation of pathogenic microorganisms (less than 2 log
10
) is known to occur on the surfaces of leafy greens during washing. Therefore, the primary purpose of the sanitizing agent is to maintain microbial quality of postharvest processing water in order to limit cross-contamination. This study modeled viral inactivation data and quantified the free-chlorine CT values that processing facilities must meet in order to achieve the desired level of hNoV GI and GII reduction. Disinfection experiments were conducted in industrial leafy green wash water collected from a full-scale fresh produce processing facility in the United States, and hNoV GI and GII results were compared with surrogate molecular and infectivity data.
Glycolytic Functions Are Conserved in the Genome of the Wine Yeast Hanseniaspora uvarum, and Pyruvate Kinase Limits Its Capacity for Alcoholic Fermentation
Authors: Langenberg Anne-Kathrin , Bink Frauke J. , Wolff Lena , Walter Stefan , von Wallbrunn Christian , Grossmann Manfred , Heinisch Jürgen J. , Schmitz Hans-Peter
Published: September 2017

Hanseniaspora uvarum
(anamorph
Kloeckera apiculata
) is a predominant yeast on wine grapes and other fruits and has a strong influence on wine quality, even when
Saccharomyces cerevisiae
starter cultures are employed. In this work, we sequenced and annotated approximately 93% of the
H. uvarum
genome. Southern and synteny analyses were employed to construct a map of the seven chromosomes present in a type strain. Comparative determinations of specific enzyme activities within the fermentative pathway in
H. uvarum
and
S. cerevisiae
indicated that the reduced capacity of the former yeast for ethanol production is caused primarily by an ∼10-fold-lower activity of the key glycolytic enzyme pyruvate kinase. The heterologous expression of the encoding gene,
H. uvarum
PYK1
(
HuPYK1
), and two genes encoding the phosphofructokinase subunits,
HuPFK1
and
HuPFK2
, in the respective deletion mutants of
S. cerevisiae
confirmed their functional homology.

IMPORTANCE
Hanseniaspora uvarum
is a predominant yeast species on grapes and other fruits. It contributes significantly to the production of desired as well as unfavorable aroma compounds and thus determines the quality of the final product, especially wine. Despite this obvious importance, knowledge on its genetics is scarce. As a basis for targeted metabolic modifications, here we provide the results of a genomic sequencing approach, including the annotation of 3,010 protein-encoding genes, e.g., those encoding the entire sugar fermentation pathway, key components of stress response signaling pathways, and enzymes catalyzing the production of aroma compounds. Comparative analyses suggest that the low fermentative capacity of
H. uvarum
compared to that of
Saccharomyces cerevisiae
can be attributed to low pyruvate kinase activity. The data reported here are expected to aid in establishing
H. uvarum
as a non-
Saccharomyces
yeast in starter cultures for wine and cider fermentations.
Flexibility-Rigidity Coordination of the Dense Exopolysaccharide Matrix in Terrestrial Cyanobacteria Acclimated to Periodic Desiccation
Authors: Liu Wen , Cui Lijuan , Xu Haiyan , Zhu Zhaoxia , Gao Xiang
Published: September 2017

A dense exopolysaccharide (EPS) matrix is crucial for cyanobacterial survival in terrestrial xeric environments, in which cyanobacteria undergo frequent expansion and shrinkage processes during environmental desiccation-rehydration cycles. However, it is unclear how terrestrial cyanobacteria coordinate the structural dynamics of the EPS matrix upon expansion and shrinkage to avoid potential mechanical stress while benefiting from the matrix. In the present study, we sought to answer this question by investigating the gene expression, protein dynamics, enzymatic characteristics, and biological roles of WspA, an abundantly secreted protein, in the representative terrestrial cyanobacterium
Nostoc flagelliforme
. The results demonstrated that WspA is a novel β-galactosidase that facilitates softening of the EPS matrix by breaking the polysaccharide backbone under substantial moisture or facilitates the thickening and relinkage of the broken matrix during the drying process, and thus these regulations are well correlated with moisture availability or desiccation-rehydration cycles. This coordination of flexibility and rigidity of the cyanobacterial extracellular matrix may contribute to a favorable balance of cell growth and stress resistance in xeric environments.

IMPORTANCE
How the exopolysaccharide matrix is dynamically coordinated by exoproteins to cope with frequent expansion and shrinkage processes in terrestrial colonial cyanobacteria remains unclear. Here we elucidated the biochemical identity and biological roles of a dominant exoprotein in these regulation processes. Our study thus gained insight into this regulative mechanism in cyanobacteria to combat periodic desiccation. In addition, the filamentous drought-adapted cyanobacterium
Nostoc flagelliforme
serves as an ideal model for us to explore this issue in this study.
Forensic Human Identification Using Skin Microbiomes
Authors: Schmedes Sarah E. , Woerner August E. , Budowle Bruce
Published: September 2017

The human microbiome contributes significantly to the genetic content of the human body. Genetic and environmental factors help shape the microbiome, and as such, the microbiome can be unique to an individual. Previous studies have demonstrated the potential to use microbiome profiling for forensic applications; however, a method has yet to identify stable features of skin microbiomes that produce high classification accuracies for samples collected over reasonably long time intervals. A novel approach is described here to classify skin microbiomes to their donors by comparing two feature types:Propionibacterium acnespangenome presence/absence features and nucleotide diversities of stable clade-specific markers. Supervised learning was used to attribute skin microbiomes from 14 skin body sites from 12 healthy individuals sampled at three time points over a >2.5-year period with accuracies of up to 100% for three body sites. Feature selection identified a reduced subset of markers from each body site that are highly individualizing, identifying 187 markers from 12 clades. Classification accuracies were compared in a formal model testing framework, and the results of this analysis indicate that learners trained on nucleotide diversity perform significantly better than those trained on presence/absence encodings. This study used supervised learning to identify individuals with high accuracy and associated stable features from skin microbiomes over a period of up to almost 3 years. These selected features provide a preliminary marker panel for future development of a robust and reproducible method for skin microbiome profiling for forensic human identification.

IMPORTANCEA novel approach is described to attribute skin microbiomes, collected over a period of >2.5 years, to their individual hosts with a high degree of accuracy. Nucleotide diversities of stable clade-specific markers with supervised learning were used to classify skin microbiomes from a particular individual with up to 100% classification accuracy for three body sites. Attribute selection was used to identify 187 genetic markers from 12 clades which provide the greatest differentiation of individual skin microbiomes from 14 skin sites. This study performs skin microbiome profiling from a supervised learning approach and obtains high classification accuracy for samples collected from individuals over a relatively long time period for potential application to forensic human identification.
Antigen Localization Influences the Magnitude and Kinetics of Endogenous Adaptive Immune Response to Recombinant Salmonella Vaccines
Authors: Sevastsyanovich Yanina R. , Withers David R. , Marriott Claire L. , Morris Faye C. , Wells Timothy J. , Browning Douglas F. , Beriotto Irene , Ross Ewan , Ali Hossam Omar , Wardius Catherine A. , Cunningham Adam F. , Henderson Ian R. , Rossiter Amanda E.
Published: September 2017

The use of recombinant attenuated
Salmonella
vaccine (RASV) strains is a promising strategy for presenting heterologous antigens to the mammalian immune system to induce both cellular and humoral immune responses. However, studies on RASV development differ on where heterologous antigens are expressed and localized within the bacterium, and it is unclear how antigen localization modulates the immune response. Previously, we exploited the plasmid-encoded toxin (Pet) autotransporter system for accumulation of heterologous antigens in cell culture supernatant. In the present study, this Pet system was used to express early secretory antigen 6 (ESAT-6), an immunodominant and diagnostic antigen from
Mycobacterium tuberculosis
, in
Salmonella enterica
serovar Typhimurium strain SL3261. Three strains were generated, whereby ESAT-6 was expressed as a cytoplasmic (SL3261/cyto), surface-bound (SL3261/surf), or secreted (SL3261/sec) antigen. Using these RASVs, the relationship between antigen localization and immunogenicity in infected C57BL/6 mice was systematically examined. Using purified antigen and specific tetramers, we showed that mice infected with the SL3261/surf or SL3261/sec strain generated large numbers of Th1 CD4
+
ESAT-6
+
splenic T cells compared to those of mice infected with SL3261/cyto. While all mice showed ESAT-6-specific antibody responses when infected with SL3261/surf or SL3261/sec, peak total serum IgG antibody titers were reached more rapidly in mice that received SL3261/sec. Thus, how antigen is localized after production within bacteria has a more marked effect on the antibody response than on the CD4
+
T cell response, which might influence the chosen strategy to localize recombinant antigen in RASVs.
Response of suction caissons for tidal current turbine applications in soft clay to monotonic and cyclic vertical loading
Authors: Wallace Jeff F. , Rutherford Cassandra J.
Published: September 2017

In soft marine clays, suction caissons provide a foundation system for tidal current turbines that further promote the sustainable nature of the system by allowing for their removal at the end of the structure’s design life. When configured as a multipod, the moment loads resulting from the horizontal flow of water will be transferred to the suction caissons as compression–uplift loads on opposing foundation legs. The behavior of a suction caisson in soft clay was investigated at aspect ratios of 1 and 2 under monotonic and cyclic vertical loading applicable to multipod-supported tidal current turbine design. Installation and solely monotonic vertical load tests indicated lower back-calculated adhesion factor, α, values and higher back-calculated bearing capacity factor, Nc, values than design standards recommend. The capacity and stiffness response of the foundation after undergoing cyclic loading was found to be largely dependent on the magnitude of displacement the foundation underwent during cyclic loading. Additionally, a threshold of elastic foundation response was observed during cyclic loading defined by a cyclic displacement amplitude. These results indicate serviceability constraints will be critical in the design of suction caisson foundations for tidal current turbine applications.
Test fill brought to failure on soft plastic marine clay at Onsøy, Norway
Authors: Berre Toralv
Published: September 2017

A test fill at Onsøy, close to the town of Fredrikstad in Norway, was built on a very soft marine clay with in situ vane strength as low as 11 kPa and a plasticity index varying from 34 to 50. The dimensions at the bottom of the long test fill were 20 m × 60 m with a height of 2.3 m. The fill, as placed in the first stage, had a computed factor of safety against foundation failure of 1.35 based on in situ vane strength. The fill was allowed to sit for about 3 years (from 1972 to 1975) before it was, in a second stage, brought to failure in about 4.3 days by raising the height. This second stage is the subject of this paper. Back-calculation of the failure by undrained stability analysis based on in situ vane tests performed shortly before the start of the second stage, based on undrained triaxial and constant volume direct simple shear tests on specimens from tube samples taken shortly before the start of the second stage and reconsolidated to the in situ effective stresses, gave factors of safety varying from 0.88 to 1.45 depending on type of analysis. Settlement values computed at the centreline of the fill for the second stage based on the results from undrained compression triaxial tests agreed reasonably well with the field measurements.
Even low levels of spruce budworm defoliation affect mortality and ingrowth but net growth is more driven by competition
Authors: Chen Cen , Weiskittel Aaron , Bataineh Mohammad , MacLean David A.
Published: September 2017

Defoliation reduces the growth and survival of trees, but this influence can be difficult to evaluate largely because of its interplay with various stand and site factors, especially for the highly dynamic defoliation of spruce–fir (Picea–Abies) forests caused by spruce budworm (SBW; Choristoneura fumiferana (Clem.)), the primary tree defoliator in North America. In this study, we developed statistical models to evaluate the influence of SBW defoliation, while considering its interaction with various stand and site factors, on spruce–fir stand dynamics of annual volume net growth, mortality, and ingrowth. The data were collected at intervals of 1 to 3 years from 560 permanent sample plots during the last SBW outbreak (1970s–1980s) in Maine, USA, and New Brunswick, Canada. These data comprise a wide range of observations of cumulative defoliation, especially at relatively low levels, that have been largely overlooked in previous studies. Our results strongly demonstrated that even relatively low levels of cumulative defoliation were significantly related to stand-level mortality and ingrowth, while net growth was more competition driven. Additionally, these stand dynamics were found to be not significantly affected by any of the site factors evaluated. These findings were consistent for Maine and New Brunswick despite their differences in forest management and SBW outbreak histories.
Functional Semi-Blind Source Separation Identifies Primary Motor Area Without Active Motor Execution
Authors: Porcaro Camillo , Cottone Carlo , Cancelli Andrea , Salustri Carlo , Tecchio Franca
Published: September 2017

High time resolution techniques are crucial for investigating the brain in action. Here, we propose a method to identify a section of the upper-limb motor area representation (FS_M1) by means of electroencephalographic (EEG) signals recorded during a completely passive condition (FS_M1bySS). We delivered a galvanic stimulation to the median nerve and we applied to EEG the semi-Blind Source Separation (s-BSS) algorithm named Functional Source Separation (FSS). In order to prove that FS_M1bySS is part of FS_M1, we also collected EEG in a motor condition, i.e. during a voluntary movement task (isometric handgrip) and in a rest condition, i.e. at rest with eyes open and closed. In motor condition, we show that the cortico-muscular coherence (CMC) of FS_M1bySS does not differ from FS_ M1 CMC (0.04 for both sources). Moreover, we show that the FS_M1bySS’s ongoing whole band activity during Motor and both rest conditions displays high mutual information and time correlation with FS_M1 (above 0.900 and 0.800, respectively) whereas much smaller ones with the primary somatosensory cortex [Formula: see text] (about 0.300 and 0.500, [Formula: see text]). FS_M1bySS as a marker of the upper-limb FS_M1 representation obtainable without the execution of an active motor task is a great achievement of the FSS algorithm, relevant in most experimental, neurological and psychiatric protocols.
Influence of modification of gravity on spherical wormhole models
Authors: Yousaf Z. , Ilyas M. , Bhatti M. Z.
Published: September 2017

This paper explores some wormhole (WH) solutions in the background of additional matter contents of f(R, T) modified gravity. For this purpose, we have considered WH geometry filled with two physically different fluid configurations: one is anisotropic and another is anisotropic characterized by the barotropic equation of state. The energy conditions are examined with particular modified gravity model and found the existence of WH solutions even in the absence of exotic matter. Also, we have analyzed the behavior of shape function in this framework. The stability and physical existence of these solutions is studied with different fluid configurations. We conclude that in the absence of exotic matter, one can find WH solutions with particular model of modified gravity.
Endomorphism algebras of Gorenstein projective modules
Authors: Zhang Aiping
Published: September 2017

Let [Formula: see text] be an Artin algebra, [Formula: see text] be a Gorenstein projective [Formula: see text]-module and [Formula: see text]. We give a characterization of modules on [Formula: see text] and show that if [Formula: see text] is [Formula: see text]-representation-finite, then [Formula: see text] is also [Formula: see text]-representation-finite. As an application, we prove if [Formula: see text] is a CM-finite [Formula: see text]-Gorenstein algebra, then [Formula: see text] is a [Formula: see text]-Igusa-Todorov algebra.
Theoretical insight into the cocrystal explosive of 2,4,6,8,10,12-hexanitrohexaazaisowurtzitane (CL-20)/1-Methyl-4,5-dinitro-1H-imidazole (MDNI)
Authors: Wu Chunlei , Zhang Shuhai , Ren Fude , Gou Ruijun , Han Gang
Published: September 2017

Cocrystal explosive is getting more and more attention in high energy density material field. Different molar ratios of 2,4,6,8,10,12-hexanitrohexaazaisowurtzitane (CL-20)/1-Methyl-4,5-dinitro-1H-imidazole (MDNI) cocrystal were studied by molecular dynamics (MD) simulation and quantum-chemical density functional theory (DFT) calculation. Binding energy of CL-20/MDNI cocrystal and radial distribution function (RDF) were used to estimate the interaction. Mechanical properties were calculated to predict the elasticity and ductility. The length and bond dissociation energy of trigger bond, surface electrostatic potentials (ESP) of CL-20/MDNI framework were calculated at B3LYP/6-311[Formula: see text]G(d,p) level. The results indicate that CL-20/MDNI cocrystal explosive might have better mechanical properties and stability in a molar ratio 3:2. The N–NO2 bond becomes stronger upon the formation of intermolecular H-bonding interaction. The surface electrostatic potential further confirms that the sensitivity decreases in cocrystal explosive in comparison with that in isolated CL-20. The oxygen balance (OB), heat of detonation ([Formula: see text], detonation velocity ([Formula: see text] and detonation pressure ([Formula: see text] of CL-20/MDNI suggest that the CL-20/MDNI cocrystal possesses excellent detonation performance and low sensitivity.
Separability and entanglement of two qubits density matrices using Lorentz transformations
Authors: Ben-Aryeh Y. , Mann A.
Published: September 2017

Explicit separability of general two qubits density matrices is related to Lorentz transformations. We use the 4-dimensional form [Formula: see text] of the Hilbert–Schmidt (HS) decomposition of the density matrix. For the generic case, in which Lorentz transformations diagonalize [Formula: see text] into [Formula: see text], we give relations between the [Formula: see text] and the [Formula: see text]. In particular, we consider two cases: (a) Two qubits density matrices with one pair of linear terms in the HS decomposition. (b) Two qubits density matrices with two or three symmetric pairs of linear terms. Some of the theoretical results are demonstrated by numerical calculations. The four non-generic cases (which may be reduced to case (a) are analyzed and the non-generic property is related explicitly to Lorentz velocity [Formula: see text] which is not reachable physically.
Characterization of Hydroporphyrins Covalently Attached to Si(100)
Authors: Jiao Jieying , Yu Miao , Holten Dewey , Lindsey Jonathan S. , Bocian David F.
Published: September 2017

Attachment of synthetic analogs of natural tetrapyrroles to electroactive surfaces enables physicochemical interrogation and may provide material for use in catalysis, diagnostics, and energy conversion. Six synthetic zinc chlorins and one free base bacteriochlorin, tailored analogs of chlorophyll and bacteriochlorophyll, respectively, have been attached to Si(100) via a high-temperature (400°C) baking method. The hydroporphyrins bear diverse functional groups that enable surface attachment (vinyl, acetyl, triisopropylsilylethynyl, pentafluorophenyl, and hydroxymethylphenyl) and a geminal dimethyl group in each reduced ring for stabilization toward adventitious dehydrogenation. The films were examined by cyclic voltammetry, FTIR spectroscopy, X-ray photoelectron spectroscopy, and ellipsometry. Monofunctionalized and difunctionalized hydroporphyrins gave monolayer and multilayer films, respectively, indicating robustness of the hydroporphyrin molecules, but in each case the film was more heterogeneous than observed with comparable porphyrins. The data suggest that some amount of unattached molecules remain intercalated with surface-attached molecules. Additional molecular designs will need to be examined to develop a deep understanding of the structure-activity relationship for formation of homogeneous monolayers and multilayers of synthetic hydroporphyrins.
On the coefficients of symmetric power L-functions
Authors: Meher Jaban , Shankhadhar Karam Deo , Viswanadham G. K.
Published: September 2017

We study the signs of the Fourier coefficients of a newform. Let [Formula: see text] be a normalized newform of weight [Formula: see text] for [Formula: see text]. Let [Formula: see text] be the [Formula: see text]th Fourier coefficient of [Formula: see text]. For any fixed positive integer [Formula: see text], we study the distribution of the signs of [Formula: see text], where [Formula: see text] runs over all prime numbers. We also find out the abscissas of absolute convergence of two Dirichlet series with coefficients involving the Fourier coefficients of cusp forms and the coefficients of symmetric power [Formula: see text]-functions.
The role of the Devonian Weardale Granite in the emplacement of the North Pennine mineralization
Authors: Bott Martin H. P. , Smith Frederick W.
Published: September 2017

After initial mapping of the fluorite/barite zones (1926) then discovery of the underlying unexposed Weardale Granite (1953), and proving its early Devonian age by the Rookhope borehole, extensive geochemical/mineralogical investigations indicate a likely alkali magmatic contribution to the post-Whin Sill orefield, contrasting with most other Hercynian Mississippi-type orefields in UK. Creaney's mapping of rank of early Namurian coals above the two central cupolas of the granite implied high temperatures of over 200°C just prior to the Whin Sill emplacement (297.4 Ma) in concord with an underlying magmatic source lasting 1 – 5 Ma. Their sharp boundaries unequivocally indicate that heat rose through the granite by hydrothermal convection, not conduction. A Stephanian source of quartz-tholeiitic magma is consistent with the Scottish Midland Valley succession (302 – 295 Ma) and contemporaneous Whin magmatism. The magma underplated the granite because of its higher density. It prepared conditions for the subsequent post-Whin Sill emplacement of the mineral deposits, producing the hot convection cell which drew in saline fluids from adjacent deep Carboniferous troughs. Following Whin Sill emplacement, highly pressurized early Permian alkali basaltic magma also underplated the granite. This was contemporaneous with the succession in the Scottish Midland Valley (age 298 – 292 Ma). Hot mineralizing fluids were forced upwards into the established convection cell in the granite and then into the Carboniferous of the Fluorite Zone, forming the mineral deposits, and then outwards beyond the granite cupola regions to deposit barite at
c
. 50°C.
Cretaceous geological evolution of the Pontides
Authors: Tüysüz Okan
Published: September 2017

The Pontides forming the southern continental margin of the Black Sea consist of the Strandja, İstanbul and Sakarya zones. The Zonguldak-Ulus Basin, located in the NE part of the İstanbul Zone, has traditionally been viewed as opening during the Barremian and deepening until the Albian under the control of normal faults. New outcrop data indicate that the southern and eastern parts of this basin facing towards the Intra-Pontide Ocean in the south were already open during the Berriasian or earlier. Uplift and erosion of the Zonguldak-Ulus Basin during the Cenomanian is attributed to collision of the İstanbul and the Sakarya zones along the Intra-Pontide Suture. The Sinop Basin in the Sakarya Zone opened during Hauterivian–Barremian time. Sedimentation in this basin continued in a deepening environment until the development of the Pontide Magmatic Belt during the Turonian. The contact between the İstanbul and the Sakarya zones is represented by a shear zone that consists of siliciclastic distal turbidites, debris-flow deposits and radiolarian cherts imbricated with Middle Jurassic–Lower Cretaceous magmatic arc fragments. This shear zone is interpreted as being the eastern continuation of the Intra-Pontide Suture, separating the İstanbul and the Sakarya zones.

The Western Black Sea Basin to the north of the Pontides possibly opened in two stages. In the first stage, coeval with the opening of the Zonguldak-Ulus Basin, the rifting was a wide-rift style and caused thinning of the continental crust. During the Turonian–Santonian, the Pontide Magmatic Belt started to develop as an extensional arc, and caused break-up of the already thinned crust and the start of oceanic spreading in the Western Black Sea Basin.
How to implement any concurrent data structure for modern servers
Authors: Calciu Irina , Sen Siddhartha , Balakrishnan Mahesh , Aguilera Marcos K.
Published: September 2017

In this paper, we propose a method to implement any concurrent data structure. Our method produces implementations that work particularly well in non-uniform memory access (NUMA) machines. Due to recent architecture trends, highly concurrent servers today are NUMA machines, where the cost of accessing a memory location is not the same across every core. To fully leverage these machines, programmers need efficient concurrent data structures that are aware of the NUMA performance artifacts.We propose Node Replication (NR), a black-box approach to obtaining such data structures. NR takes an arbitrary sequential data structure and automatically transforms it into a NUMA-aware concurrent data structure satisfying linearizability. Using NR requires no expertise in concurrent data structure design, and the result is free of concurrency bugs. NR draws ideas from two disciplines: shared-memory algorithms and distributed systems. Briefly, NR implements a NUMA-aware shared log, and then uses the log to replicate data structures consistently across NUMA nodes. The cost of NR is additional memory for its log and replicas.
Regulating Bacterial Virulence with RNA
Authors: Quereda Juan J. , Cossart Pascale
Published: September 2017

Noncoding RNAs (ncRNAs) regulating virulence have been identified in most pathogens. This review discusses RNA-mediated mechanisms exploited by bacterial pathogens to successfully infect and colonize their hosts. It discusses the most representative RNA-mediated regulatory mechanisms employed by two intracellular [Listeria monocytogenes and Salmonella enterica serovar Typhimurium (S. Typhimurium)] and two extracellular (Vibrio cholerae and Staphylococcus aureus) bacterial pathogens. We review the RNA-mediated regulators (e.g., thermosensors, riboswitches, cis- and trans-encoded RNAs) used for adaptation to the specific niches colonized by these bacteria (intestine, blood, or the intracellular environment, for example) in the framework of the specific pathophysiological aspects of the diseases caused by these microorganisms. A critical discussion of the newest findings in the field of bacterial ncRNAs shows how examples in model pathogens could pave the way for the discovery of new mechanisms in other medically important bacterial pathogens.
Neisseria gonorrhoeae: Drug Resistance, Mouse Models, and Vaccine Development
Authors: Rice Peter A. , Shafer William M. , Ram Sanjay , Jerse Ann E.
Published: September 2017

Gonorrhea, an obligate human infection, is on the rise worldwide and gonococcal strains resistant to many antibiotics are emerging. Appropriate antimicrobial treatment and prevention, including effective vaccines, are urgently needed. To guide investigation, an experimental model of genital tract infection has been developed in female mice to study mechanisms by which Neisseria gonorrhoeae evades host-derived antimicrobial factors and to identify protective and immunosuppressive pathways. Refinements of the animal model have also improved its use as a surrogate host of human infection and accelerated the testing of novel therapeutic and prophylactic compounds against gonococcal infection. Reviewed herein are the (a) history of antibiotic usage and resistance against gonorrhea and the consequences of resistance mechanisms that may increase gonococcal fitness and therefore the potential for spread, (b) use of gonococcal infection in the animal model system to study mechanisms of pathogenesis and host defenses, and (c) current status of vaccine development.
Bacterial Cell Size: Multifactorial and Multifaceted
Authors: Westfall Corey S. , Levin Petra Anne
Published: September 2017

How cells establish, maintain, and modulate size has always been an area of great interest and fascination. Until recently, technical limitations curtailed our ability to understand the molecular basis of bacterial cell size control. In the past decade, advances in microfluidics, imaging, and high-throughput single-cell analysis, however, have led to a flurry of work revealing size to be a highly complex trait involving the integration of three core aspects of bacterial physiology: metabolism, growth, and cell cycle progression.
Age- and strain-related aberrant Ca2+release is associated with sudden cardiac death in theACTCE99K mouse model of hypertrophic cardiomyopathy
Authors: Rowlands Christina T. , Owen Thomas , Lawal Saheed , Cao Shuangyi , Pandey Samata S. , Yang Hsiang-Yu , Song Weihua , Wilkinson Ross , Alvarez-Laviada Anita , Gehmlich Katja , Marston Steven B. , MacLeod Kenneth T.
Published: September 2017

Patients with hypertrophic cardiomyopathy, particularly young adults, can die from arrhythmia, but the mechanism underlying abnormal rhythm formation remains unknown. C57Bl6 × CBA/Ca mice carrying a cardiac actin ( ACTC) E99K (Glu99Lys) mutation reproduce many aspects of human hypertrophic cardiomyopathy, including increased myofilament Ca2+sensitivity and sudden death in a proportion (up to 40%) of young (28−40 day old) animals. We studied the hearts of transgenic (TG; ACTC E99K) mice and their non-TG (NTG) littermates when they were in their vulnerable period (28–40 days old) and when they were adult (8–12 wk old). Ventricular myocytes were isolated from the hearts of TG and NTG mice at these two time points. We also examined the hearts of mice that died suddenly (SCD). SCD animals had approximately four times more collagen compared with age-matched NTG mice, yet myocyte cell size was normal. Young TG mice had double the collagen content of NTG mice. Contraction and Ca2+transients were greater in cells from young TG mice compared with their NTG littermates but not in cells from adult mice (TG or NTG). Cells from young TG mice had a greater propensity for Ca2+waves than NTG littermates, and, despite similar sarcoplasmic reticulum Ca2+content, a proportion of these cells had larger Ca2+spark mass. We found that the probability of SCD in young TG mice was increased when the mutation was expressed in animals with a CBA/Ca2+background and almost eliminated in mice bred on a C57Bl6 background. The latter TG mice had normal cellular Ca2+homeostasis.

NEW & NOTEWORTHY Mice with the actin Glu99Lys hypertrophic cardiomyopathy mutation ( ACTC E99K) are prone to sudden cardiac death around 40 days, associated with increased Ca2+transients, spark mass, and fibrosis. However, adult survivors have normal Ca2+transients and spark density accompanied by hypertrophy. Penetrance of the sudden cardiac death phenotype depends on the genetic background of the mouse.

Listen to this article’s corresponding podcast at http://ajpheart.podbean.com/e/calcium-regulation-in-e99k-mouse-heart/ .
Research on Predicting the Rutting of Asphalt Pavement Based on a Simplified Burgers Creep Model
Authors: Lian-sheng Gao , Han-cheng Dan , Jia-qi Chen
Published: September 2017

Rutting is one of the most important distresses for asphalt pavement structures especially due to the heavy traffic loadings. In this paper, the solution of Burgers model is employed and simplified, which makes the residual strain only depend on the applied load. Then, the governing equation for dynamic response of pavement was established and a semianalytical solution related to the stress state of asphalt pavement was obtained. Further, an explicit expression was presented and validated to calculate rutting depth of asphalt pavement through incorporating the dynamic stress solution, simplified Burgers model solution, and time hardening model. Compared with the FEM method, the calculation error is less than 5%, which proved the method proposed to be feasible. Compared with the numerical simulation method, every derivation of the rutting formula in this paper has the clear physical meaning and is hence easy to be understood. Besides, the proposed method can save a significant amount of time consumed due to its fast and reliable calculation.
An Exploration of Changes in the Measurement of Mammography in the National Health Interview Survey
Authors: Gonzales Felisa A. , Willis Gordon B. , Breen Nancy , Yan Ting , Cronin Kathy A. , Taplin Stephen H. , Yu Mandi
Published: September 2017

Background: Using the National Health Interview Survey (NHIS), we examined the effect of question wording on estimates of past-year mammography among racially/ethnically diverse women ages 40–49 and 50–74 without a history of breast cancer.

Methods: Data from one-part (“Have you had a mammogram during the past 12 months?”) and two-part (“Have you ever had a mammogram”; “When did you have your most recent mammogram?”) mammography history questions administered in the 2008, 2011, and 2013 NHIS were analyzed. χ2 tests provided estimates of changes in mammography when question wording was either the same (two-part question) or differed (two-part question followed by one-part question) in the two survey years compared. Crosstabulations and regression models assessed the type, extent, and correlates of inconsistent responses to the two questions in 2013.

Results: Reports of past-year mammography were slightly higher in years when the one-part question was asked than when the two-part question was asked. Nearly 10% of women provided inconsistent responses to the two questions asked in 2013. Black women ages 50 to 74 [adjusted OR (aOR), 1.50; 95% confidence interval (CI), 1.16–1.93] and women ages 40–49 in poor health (aOR, 2.22; 95% CI, 1.09–4.52) had higher odds of inconsistent responses; women without a usual source of care had lower odds (40–49: aOR, 0.42; 95% CI, 0.21–0.85; 50–74: aOR, 0.42; 95% CI, 0.24–0.74).

Conclusions: Self-reports of mammography are sensitive to question wording. Researchers should use equivalent questions that have been designed to minimize response biases such as telescoping and social desirability.

Impact: Trend analyses relying on differently worded questions may be misleading and conceal disparities. Cancer Epidemiol Biomarkers Prev; 26(11); 1611–8. ©2017 AACR.
Biomarker-Stratified Phase III Clinical Trials: Enhancement with a Subgroup-Focused Sequential Design
Authors: Matsui Shigeyuki , Crowley John
Published: September 2017

Among various design approaches to phase III clinical trials with a predictive biomarker, the marker-stratified all-comers design is advantageous because it allows for establishing the utility of both treatment and biomarker, but it is often criticized for requiring large sample sizes, as the design includes both marker-positive and marker-negative patients. In this article, we propose a simple but flexible subgroup-focused design for marker-stratified trials that allow both sequential assessment across marker-defined subgroups and adaptive subgroup selection while retaining an assessment using the entire patient cohort at the final analysis stage, possibly using established marker-based multiple testing procedures. Numerical evaluations indicate that the proposed marker-stratified design has a robustness property in preserving statistical power for detecting various profiles of treatment effects across the subgroups while effectively reducing the number of randomized patients in the marker-negative subgroup with presumably limited treatment efficacy. In contrast, the traditional all-comers and sequential enrichment designs could suffer from low statistical power for some possible profiles of treatment effects. The latter also needs long study durations and a large number of marker-screened patients. We also provide an application to SWOG S0819, a trial to assess the role of cetuximab in treating non–small cell lung cancers. These evaluations indicate that the proposed subgroup-focused approach can enhance the efficiency of the marker-stratified design for definitive evaluation of treatment and biomarker in phase III clinical trials. Clin Cancer Res; 24(5); 994–1001. ©2017 AACR.
Associations between Liver Enzyme Levels and Parameters of the Metabolic Syndrome in Obese Children
Authors: Hampe Christiane S. , Shaffer Michele L. , Roth Christian L.
Published: September 2017

Background: Obesity is strongly associated with insulin resistance, hypertension, dyslipidemia, and therefore risk for metabolic syndrome (MetS), which is an increasing problem in youth. The potential role of elevated liver enzyme levels in this context needs to be further investigated. Methods: This paper provides a post hoc analysis of a cross-sectional study of 77 obese nondiabetic children (51% female; median age 11.7 years; BMI >97th percentile) enrolled at the University of Bonn, Bonn, Germany. Anthropometric parameters, lipid profiles, glycemic control, and liver enzyme levels were evaluated. Glucose and insulin levels were determined during an oral glucose tolerance test (OGTT). Gender- and age-specific cutoff values were used to assess MetS. Results: A high prevalence of hypertension (51%), dyslipidemia (52%), elevated liver enzyme levels (51%), and hyperglycemia (24%) was found. There was considerable overlap between the presence of different MetS risk factors in individuals, and 40% of the participants had ≥3 of a maximum of 5 MetS risk factors. Elevated liver enzyme levels were significantly associated with reduced insulin sensitivity, as the OGTT-insulin response was significantly higher in participants with elevated transaminases (p = 0.01). This association was independent of hyperglycemia and dyslipidemia (p = 0.03). Conclusions: We conclude that liver enzyme levels are related to insulin sensitivity in obese children and could therefore be an indirect indicator for MetS. Testing for disturbed glucose metabolism should be considered for obese children with elevated liver enzymes.
Technical Considerations on Phase Mapping for Identification of Atrial Reentrant Activity in Direct- and Inverse-Computed Electrograms
Authors: Rodrigo Miguel , Climent Andreu M. , Liberos Alejandro , Fernández-Avilés Francisco , Berenfeld Omer , Atienza Felipe , Guillem Maria S.
Published: September 2017

Background:

Phase mapping has become a broadly used technique to identify atrial reentrant circuits for ablative therapy guidance. This work studies the phase mapping process and how the signal nature and its filtering affect the reentrant pattern characterization in electrogram (EGM), body surface potential mapping, and electrocardiographic imaging signals.

Methods and Results:

EGM, body surface potential mapping, and electrocardiographic imaging phase maps were obtained from 17 simulations of atrial fibrillation, atrial flutter, and focal atrial tachycardia. Reentrant activity was identified by singularity point recognition in raw signals and in signals after narrow band-pass filtering at the highest dominant frequency (HDF). Reentrant activity was dominantly present in the EGM recordings only for atrial fibrillation and some atrial flutter propagations patterns, and HDF filtering allowed increasing the reentrant activity detection from 60% to 70% of time in atrial fibrillation in unipolar recordings and from 0% to 62% in bipolar. In body surface potential mapping maps, HDF filtering increased from 10% to 90% the sensitivity, although provoked a residual false reentrant activity ≈30% of time. In electrocardiographic imaging, HDF filtering allowed to increase ≤100% the time with detected rotors, although provoked the apparition of false rotors during 100% of time. Nevertheless, raw electrocardiographic imaging phase maps presented reentrant activity just in atrial fibrillation recordings accounting for ≈80% of time.

Conclusions:

Rotor identification is accurate and sensitive and does not require additional signal processing in measured or noninvasively computed unipolar EGMs. Bipolar EGMs and body surface potential mapping do require HDF filtering to detect rotors at the expense of a decreased specificity.
Prognostic Value of Aortic Stiffness in Patients After ST‐Elevation Myocardial Infarction
Authors: Feistritzer Hans‐Josef , Klug Gert , Reinstadler Sebastian J. , Reindl Martin , Niess Lea , Nalbach Timo , Kremser Christian , Mayr Agnes , Metzler Bernhard
Published: September 2017

Background

High aortic stiffness has been shown to be a strong predictor of morbidity and mortality in the general population and several patient cohorts. However, in patients after
ST
‐elevation myocardial infarction, the prognostic value of high aortic stiffness is unknown so far.

Methods and Results

This prospective observational study included 160 consecutive patients with first acute
ST
‐elevation myocardial infarction. Aortic pulse wave velocity (
PWV
) was measured 2 (interquartile range 2‐4 days) days after infarction using cardiac magnetic resonance imaging. The primary end point was defined as a composite end point of major adverse cardiac and cerebrovascular events (
MACCE
) comprising death, nonfatal myocardial reinfarction, new congestive heart failure, and stroke. During a median follow‐up of 1.2 years (interquartile range 1.0‐3.1 years), 19 (12%)
MACCE
events occurred. Kaplan‐Meier analysis showed a significantly lower
MACCE
‐free survival in patients with high
PWV
(
PWV
>7.3 m/s, log‐rank
P
=0.003). Multivariable Cox regression analysis revealed
PWV
>7.3 m/s to be an independent predictor of
MACCE
after adjustment for age, sex, mean blood pressure, N‐terminal pro–brain natriuretic peptide levels, presence of multivessel disease, and left ventricular stroke volume (hazard ratios ≥3.5; 95% confidence interval 1.4‐13.3; all
P
≤0.018). In reclassification analysis the addition of
PWV
to a risk model comprising major clinical prognostic parameters led to a net reclassification improvement of 0.11 (95% confidence interval 0.06‐0.17;
P
<0.001).

Conclusions

Increased aortic stiffness is an independent predictor of
MACCE
after acute
ST
‐elevation myocardial infarction. Moreover, the assessment of aortic stiffness in addition to classical risk factors significantly improved early risk stratification.