bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of Transport Properties Effect on the Performance of Gas-Condensate Reservoirs Using Compositional Simulation
Authors: Al Ghamdi Bander N. , Ayala H. Luis F.
Published: February 2017

Gas-condensate productivity is highly dependent on the thermodynamic behavior of the fluids-in-place. The condensation attendant with the depletion of gas-condensate reservoirs leads to a deficiency in the flow of fluids moving toward the production channels. The impairment is a result of condensate accumulation near the production channels in an immobility state until reaching a critical saturation point. Considering the flow phenomenon of gas-condensate reservoirs, tight formations can be inevitably complex hosting environments in which to achieve economical production. This work is aimed to assess the productivity gas-condensate reservoirs in a naturally fractured setting against the effect of capillary pressure and relative permeability constraints. The severity of condensate coating and magnitude of impairment was evaluated in a system with a permeability of 0.001 mD using an in-house compositional simulator. Several composition combinations were considered to portray mixtures ascending in complexity from light to heavy. The examination showed that thicker walls of condensate and greater impairment are attained with mixture containing higher nonvolatile concentrations. In addition, the influence of different capillary curves was insignificant to the overall behavior of fluids-in-place and movement within the pores medium. A greater impact on the transport of fluids was owed to relative permeability curves, which showed dependency on the extent of condensate content. Activating diffusion was found to diminish flow constraints due to the capturing of additional extractions that were not accounted for under Darcy's law alone.
Strain and vector magnetic field tuning of the anomalous phase in Sr
3
Ru
2
O
7
Authors: Brodsky Daniel O. , Barber Mark E. , Bruin Jan A. N. , Borzi Rodolfo A. , Grigera Santiago A. , Perry Robin S. , Mackenzie Andrew P. , Hicks Clifford W.
Published: February 2017

The components of the field-induced order in Sr
3
Ru
2
O
7
coexist microscopically, not, as has long been thought, in domains.
Homolactic Acid Fermentation by the Genetically Engineered Thermophilic Homoacetogen Moorella thermoacetica ATCC 39073
Authors: Iwasaki Yuki , Kita Akihisa , Yoshida Koichiro , Tajima Takahisa , Yano Shinichi , Shou Tomohiro , Saito Masahiro , Kato Junichi , Murakami Katsuji , Nakashimada Yutaka
Published: February 2017

For the efficient production of target metabolites from carbohydrates, syngas, or H
2
-CO
2
by genetically engineered
Moorella thermoacetica
, the control of acetate production (a main metabolite of
M. thermoacetica
) is desired. Although propanediol utilization protein (PduL) was predicted to be a phosphotransacetylase (PTA) involved in acetate production in
M. thermoacetica
, this has not been confirmed. Our findings described herein directly demonstrate that two putative PduL proteins, encoded by Moth_0864 (
pduL1
) and Moth_1181 (
pduL2
), are involved in acetate formation as PTAs. To disrupt these genes, we replaced each gene with a lactate dehydrogenase gene from
Thermoanaerobacter pseudethanolicus
ATCC 33223 (
T-ldh
). The acetate production from fructose as the sole carbon source by the
pduL1
deletion mutant was not deficient, whereas the disruption of
pduL2
significantly decreased the acetate yield to approximately one-third that of the wild-type strain. The double-deletion (both
pduL
genes) mutant did not produce acetate but produced only lactate as the end product from fructose. These results suggest that both
pduL
genes are associated with acetate formation via acetyl-coenzyme A (acetyl-CoA) and that their disruption enables a shift in the homoacetic pathway to the genetically synthesized homolactic pathway via pyruvate.

IMPORTANCE
This is the first report, to our knowledge, on the experimental identification of PTA genes in
M. thermoacetica
and the shift of the native homoacetic pathway to the genetically synthesized homolactic pathway by their disruption on a sugar platform.
Revisiting the Regulation of the Primary Scaffoldin Gene in Clostridium thermocellum
Authors: Ortiz de Ora Lizett , Muñoz-Gutiérrez Iván , Bayer Edward A. , Shoham Yuval , Lamed Raphael , Borovok Ilya
Published: February 2017

Cellulosomes are considered to be one of the most efficient systems for the degradation of plant cell wall polysaccharides. The central cellulosome component comprises a large, noncatalytic protein subunit called scaffoldin. Multiple saccharolytic enzymes are incorporated into the scaffoldins via specific high-affinity cohesin-dockerin interactions. Recently, the regulation of genes encoding certain cellulosomal components by multiple RNA polymerase alternative σ
I
factors has been demonstrated in
Clostridium
(
Ruminiclostridium
)
thermocellum
. In the present report, we provide experimental evidence demonstrating that the
C. thermocellum cipA
gene, which encodes the primary cellulosomal scaffoldin, is regulated by several alternative σ
I
factors and by the vegetative σ
A
factor. Furthermore, we show that previously suggested transcriptional start sites (TSSs) of
C. thermocellum cipA
are actually posttranscriptional processed sites. By using comparative bioinformatic analysis, we have also identified highly conserved σ
I
- and σ
A
-dependent promoters upstream of the primary scaffoldin-encoding genes of other clostridia, namely,
Clostridium straminisolvens
,
Clostridium clariflavum
,
Acetivibrio cellulolyticus
, and
Clostridium
sp. strain Bc-iso-3. Interestingly, a previously identified TSS of the primary scaffoldin CbpA gene of
Clostridium cellulovorans
matches the predicted σ
I
-dependent promoter identified in the present work rather than the previously proposed σ
A
promoter. With the exception of
C. cellulovorans
, both σ
I
and σ
A
promoters of primary scaffoldin genes are located more than 600 nucleotides upstream of the start codon, yielding long 5′-untranslated regions (5′-UTRs). Furthermore, these 5′-UTRs have highly conserved stem-loop structures located near the start codon. We propose that these large 5′-UTRs may be involved in the regulation of both the primary scaffoldin and other cellulosomal components.

IMPORTANCE
Cellulosome-producing bacteria are among the most effective cellulolytic microorganisms known. This group of bacteria has biotechnological potential for the production of second-generation biofuels and other biocommodities from cellulosic wastes. The efficiency of cellulose hydrolysis is due to their cellulosomes, which arrange enzymes in close proximity on the cellulosic substrate, thereby increasing synergism among the catalytic domains. The backbone of these multienzyme nanomachines is the scaffoldin subunit, which has been the subject of study for many years. However, its genetic regulation is poorly understood. Hence, from basic and applied points of view, it is imperative to unravel the regulatory mechanisms of the scaffoldin genes. The understanding of these regulatory mechanisms can help to improve the performance of the industrially relevant strains of
C. thermocellum
and related cellulosome-producing bacteria
en route
to the consolidated bioprocessing of biomass.
Microaerophilic Fe(II)-Oxidizing Zetaproteobacteria Isolated from Low-Fe Marine Coastal Sediments: Physiology and Composition of Their Twisted Stalks
Authors: Laufer K. , Nordhoff M. , Halama M. , Martinez R. E. , Obst M. , Nowak M. , Stryhanyuk H. , Richnow H. H. , Kappler A.
Published: February 2017

Microaerophilic Fe(II) oxidizers are commonly found in habitats containing elevated Fe(II) and low O
2
concentrations and often produce characteristic Fe mineral structures, so-called twisted stalks or tubular sheaths. Isolates originating from freshwater habitats are all members of the
Betaproteobacteria
, while isolates from marine habitats belong almost exclusively to the
Zetaproteobacteria
. So far, only a few isolates of marine microaerophilic Fe(II) oxidizers have been described, all of which are obligate microaerophilic Fe(II) oxidizers and have been thought to be restricted to Fe-rich systems. Here, we present two new isolates of marine microaerophilic Fe(II)-oxidizing
Zetaproteobacteria
that originate from typical coastal marine sediments containing only low Fe concentrations (2 to 11 mg of total Fe/g of sediment [dry weight]; 70 to 100 μM dissolved Fe
2+
in the porewater). The two novel
Zetaproteobacteria
share characteristic physiological properties of the
Zetaproteobacteria
group, even though they come from low-Fe environments: the isolates are obligate microaerophilic Fe(II) oxidizers and, like most isolated
Zetaproteobacteria
, they produce twisted stalks. We found a low organic carbon content in the stalks (∼0.3 wt%), with mostly polysaccharides and saturated aliphatic chains (most likely lipids). The Fe minerals in the stalks were identified as lepidocrocite and possibly ferrihydrite. Immobilization experiments with Ni
2+
showed that the stalks can function as a sink for trace metals. Our findings show that obligate microaerophilic Fe(II) oxidizers belonging to the
Zetaproteobacteria
group are not restricted to Fe-rich environments but can also be found in low-Fe marine environments, which increases their overall importance for the global biogeochemical Fe cycle.

IMPORTANCE
So far, only a few isolates of benthic marine microaerophilic Fe(II) oxidizers belonging to the
Zetaproteobacteria
exist, and most isolates were obtained from habitats containing elevated Fe concentrations. Consequently, it was thought that these microorganisms are important mainly in habitats with high Fe concentrations. The two novel isolates of
Zetaproteobacteria
that are presented in the present study were isolated from typical coastal marine sediments that do not contain elevated Fe concentrations. This increases the knowledge about possible habitats in which
Zetaproteobacteria
can exist. Furthermore, we show that the physiology and the typical organo-mineral structures (twisted stalks) that are produced by the isolates do not notably differ from the physiology and the cell-mineral structures of isolates from environments with high Fe concentrations. We also showed that the organo-mineral structures can function as a sink for trace metals.
Evolution of Pectobacterium Bacteriophage ΦM1 To Escape Two Bifunctional Type III Toxin-Antitoxin and Abortive Infection Systems through Mutations in a Single Viral Gene
Authors: Blower Tim R. , Chai Ray , Przybilski Rita , Chindhy Shahzad , Fang Xinzhe , Kidman Samuel E. , Tan Hui , Luisi Ben F. , Fineran Peter C. , Salmond George P. C.
Published: February 2017

Some bacteria, when infected by their viral parasites (bacteriophages), undergo a suicidal response that also terminates productive viral replication (abortive infection [Abi]). This response can be viewed as an altruistic act protecting the uninfected bacterial clonal population. Abortive infection can occur through the action of type III protein-RNA toxin-antitoxin (TA) systems, such as ToxIN
Pa
from the phytopathogen
Pectobacterium atrosepticum
. Rare spontaneous mutants evolved in the generalized transducing phage ΦM1, which escaped ToxIN
Pa
-mediated abortive infection in
P. atrosepticum
. ΦM1 is a member of the
Podoviridae
and a member of the “KMV-like” viruses, a subset of the T7 supergroup. Genomic sequencing of ΦM1 escape mutants revealed single-base changes which clustered in a single open reading frame. The “escape” gene product, M1-23, was highly toxic to the host bacterium when overexpressed, but mutations in M1-23 that enabled an escape phenotype caused M1-23 to be less toxic. M1-23 is encoded within the DNA metabolism modular section of the phage genome, and when it was overexpressed, it copurified with the host nucleotide excision repair protein UvrA. While the M1-23 protein interacted with UvrA in coimmunoprecipitation assays, a UvrA mutant strain still aborted ΦM1, suggesting that the interaction is not critical for the type III TA Abi activity. Additionally, ΦM1 escaped a heterologous type III TA system (TenpIN
Pl
) from
Photorhabdus luminescens
(reconstituted in
P. atrosepticum
) through mutations in the same protein, M1-23. The mechanistic action of M1-23 is currently unknown, but further analysis of this protein may provide insights into the mode of activation of both systems.

IMPORTANCE
Bacteriophages, the viral predators of bacteria, are the most abundant biological entities and are important factors in driving bacterial evolution. In order to survive infection by these viruses, bacteria have evolved numerous antiphage mechanisms. Many of the studies involved in understanding these interactions have led to the discovery of biotechnological and gene-editing tools, most notably restriction enzymes and more recently the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas systems. Abortive infection is another such antiphage mechanism that warrants further investigation. It is unique in that activation of the system leads to the premature death of the infected cells. As bacteria infected with the virus are destined to die, undergoing precocious suicide prevents the release of progeny phage and protects the rest of the bacterial population. This altruistic suicide can be caused by type III toxin-antitoxin systems, and understanding the activation mechanisms involved will provide deeper insight into the abortive infection process.
Temperature-Dependent Growth Modeling of Environmental and Clinical Legionella pneumophila Multilocus Variable-Number Tandem-Repeat Analysis (MLVA) Genotypes
Authors: Sharaby Yehonatan , Rodríguez-Martínez Sarah , Oks Olga , Pecellin Marina , Mizrahi Hila , Peretz Avi , Brettar Ingrid , Höfle Manfred G. , Halpern Malka
Published: February 2017

Legionella pneumophila
causes waterborne infections resulting in severe pneumonia. High-resolution genotyping of
L. pneumophila
isolates can be achieved by multiple-locus variable-number tandem-repeat analysis (MLVA). Recently, we found that different MLVA genotypes of
L. pneumophila
dominated different sites in a small drinking-water network, with a genotype-related temperature and abundance regime. The present study focuses on understanding the temperature-dependent growth kinetics of the genotypes that dominated the water network. Our aim was to model mathematically the influence of temperature on the growth kinetics of different environmental and clinical
L. pneumophila
genotypes and to compare it with the influence of their ecological niches. Environmental strains showed a distinct temperature preference, with significant differences among the growth kinetics of the three studied genotypes (Gt4, Gt6, and Gt15). Gt4 strains exhibited superior growth at lower temperatures (25 and 30°C), while Gt15 strains appeared to be best adapted to relatively higher temperatures (42 and 45°C). The temperature-dependent growth traits of the environmental genotypes were consistent with their distribution and temperature preferences in the water network. Clinical isolates exhibited significantly higher growth rates and reached higher maximal cell densities at 37°C and 42°C than the environmental strains. Further research on the growth preferences of
L. pneumophila
clinical and environmental genotypes will result in a better understanding of their ecological niches in drinking-water systems as well as in the human body.

IMPORTANCE
Legionella pneumophila
is a waterborne pathogen that threatens humans in developed countries. The bacteria inhabit natural and man-made freshwater environments. Here we demonstrate that different environmental
L. pneumophila
genotypes have different temperature-dependent growth kinetics. Moreover,
Legionella
strains that belong to the same species but were isolated from environmental and clinical sources possess adaptations for growth at different temperatures. These growth preferences may influence the bacterial colonization at specific ecological niches within the drinking-water network. Adaptations for growth at human body temperatures may facilitate the abilities of some
L. pneumophila
strains to infect and cause illness in humans. Our findings may be used as a tool to improve
Legionella
monitoring in drinking-water networks. Risk assessment models for predicting the risk of legionellosis should take into account not only
Legionella
concentrations but also the temperature-dependent growth kinetics of the isolates.
The overlooked human influence in historic and prehistoric floods in the European Alps
Authors: Brisset Elodie , Guiter Frédéric , Miramont Cécile , Troussier Tiané , Sabatier Pierre , Poher Yoann , Cartier Rosine , Arnaud Fabien , Malet Emmanuel , Anthony Edward J.
Published: February 2017

Understanding the role of climate and humans in generating mountain slope instability is crucial because such instability influences downstream fluvial activity and is a major threat to societies. Here, we use the sedimentary archive of Lake Allos (southeastern France), a mountain lake in the European Alps, to characterize mountain flood deposits and vegetation dynamics over the past 7000 yr. Our results support the interpretation of a critical threshold in catchment sensitivity to erosion at 1700 calibrated (cal.) yr B.P. (A.D. 250) probably resulting from long-term, uninterrupted impacts of human activity. The frequency and severity of floods increased dramatically after this date. These results demonstrate that underestimation of human impacts over the Holocene may pose a challenge to a clear understanding of past climate changes because paleoflood records are highly likely to have been affected by geomorphic thresholds. Natural reforestation since the end of the 19th century does not appear to be sufficient to induce a flood regime comparable to that which occurred prior to 1700 cal. yr B.P. This poses the question as to whether forest restoration in high-altitude environments is liable to foster a return to a low-erosion regime over the next decades, or whether the overall severity of soil degradation has been such as to preclude a return to previous conditions.
Aragonitic scleractinian corals in the Cretaceous calcitic sea
Authors: Janiszewska Katarzyna , Mazur Maciej , Escrig Stéphane , Meibom Anders , Stolarski Jarosław
Published: February 2017

Changes in seawater chemistry have affected the evolution of calcifying marine organisms, including their skeletal polymorph (calcite versus aragonite), which is believed to have been strongly influenced by the Mg/Ca ratio at the time these animals first emerged. However, we show that micrabaciids, a scleractinian coral clade that first appeared in the fossil record of the Cretaceous, when the ocean Mg/Ca ratio was near the lowest in the Phanerozoic (thus a priori favoring calcitic mineralogy), formed skeletons composed exclusively of aragonite. Exceptionally preserved aragonitic coralla of Micrabacia from the Late Cretaceous Ripley Formation (southeastern USA) have skeletal microstructures identical to their modern representatives. In addition, skeletons of Micrabacia from Cretaceous chalk deposits of eastern Poland are clearly diagenetically altered in a manner consistent with originally aragonitic mineralogy. These deposits have also preserved fossils of the scleractinian Coelosmilia, the skeleton of which is interpreted as originally calcitic. These findings show that if changes in seawater Mg/Ca ratio influenced the mineralogy of scleractinian corals, the outcome was taxon specific. The aragonitic mineralogy, unique skeletal microstructures and ultrastructures, and low Mg/Ca ratios in both fossil and living micrabaciids indicate that their biomineralization process is strongly controlled and has withstood major fluctuations in seawater chemistry during the past 70 m.y.
Pore fluids in Dead Sea sediment core reveal linear response of lake chemistry to global climate changes
Authors: Levy Elan J. , Stein Mordechai , Lazar Boaz , Gavrieli Ittai , Yechieli Yoseph , Sivan Orit
Published: February 2017

Pore fluids extracted from a 456 m sediment core, recovered within the framework of a multinational and International Continental Scientific Drilling Program (ICDP) co-sponsored effort at the bottom of the terminal Dead Sea, recorded the chemical variations in the deep lake over the past 220 k.y. Mg2+ and Br– were shown to be conservative in the pore fluids, increasing in concentration during interglacial periods, diluting during glacials, and providing excellent proxies for deep lake net water balance changes. Furthermore, the Na/Cl ratio recorded the process of halite precipitation and dissolution induced by these hydrological changes. Mg2+ and Br– records follow a glacial-interglacial pattern, such as observed in atmospheric CO2 concentrations and global sea-surface temperatures, albeit with a phase offset. At the end of the last interglacial (ca. 116 ka), there is a delay in onset of dilution of the deep lake, most likely due to the limnological transition from holomictic to meromictic conditions. The increase in deep lake concentrations at Last Glacial Termination I is delayed as a result of freshwater input into the deep lake during the cooler Younger Dryas period. There is a persistent relationship between precipitation in the watershed and North Atlantic sea-surface temperatures, similar to conditions observed over the past instrumental record. Deviations from the long-term trends occurred during interglacial periods, Marine Isotope Stages MIS 5e and MIS 1, when the deep Dead Sea was significantly diluted, and coincided with Mediterranean sapropel layers S5 and S1.
Prevalence and determinants of undetected dementia in the community: a systematic literature review and a meta-analysis
Authors: Lang Linda , Clifford Angela , Wei Li , Zhang Dongmei , Leung Daryl , Augustine Glenda , Danat Isaac M , Zhou Weiju , Copeland John R , Anstey Kaarin J , Chen Ruoling
Published: February 2017

Objectives

Detection of dementia is essential for improving the lives of patients but the extent of underdetection worldwide and its causes are not known. This study aimed to quantify the prevalence of undetected dementia and to examine its correlates.

Methods/setting/participants

A systematic search was conducted until October 2016 for studies reporting the proportion of undetected dementia and/or its determinants in either the community or in residential care settings worldwide. Random-effects models calculated the pooled rate of undetected dementia and subgroup analyses were conducted to identify determinants of the variation.

Primary and secondary outcome measures

The outcome measures of interest were the prevalence and determinants of undetected dementia.

Results

23 studies were eligible for inclusion in this review. The pooled rate of undetected dementia was 61.7% (95% CI 55.0% to 68.0%). The rate of underdetection was higher in China and India (vs Europe and North America), in the community setting (vs residential/nursing care), age of <70 years, male gender and diagnosis by general practitioner. However, it was lower in the studies using Mini-Mental State Examination (MMSE) diagnosis criteria.

Conclusions

The prevalence of undetected dementia is high globally. Wide variations in detecting dementia need to be urgently examined, particularly in populations with low socioeconomic status. Efforts are required to reduce diagnostic inequality and to improve early diagnosis in the community.
Cross-sectional study examining the prevalence, correlates and sequencing of electronic cigarette and tobacco use among 11–16-year olds in schools in Wales
Authors: de Lacy Elen , Fletcher Adam , Hewitt Gillian , Murphy Simon , Moore Graham
Published: February 2017

Objectives

To examine the prevalence and frequency of electronic (e)-cigarette use among young people in Wales, associations with socio-demographic characteristics, smoking and other substances and the sequencing of e-cigarette and tobacco use.

Design

A cross-sectional survey of school students in Wales undertaken in 2015.

Setting

87 secondary schools in Wales.

Participants

Students aged 11–16 (n=32 479).

Results

Overall, students were nearly twice as likely to report ever using e-cigarettes (18.5%) as smoking tobacco (10.5%). Use of e-cigarettes at least weekly was 2.7% in the whole sample, rising to 5.7% among those aged 15–16. Almost half (41.8%) of daily smokers reported being regular e-cigarette users. Regular e-cigarette use was more prevalent among current cannabis users (relative risk ratio (RRR)=41.82; 95% CI 33.48 to 52.25)), binge drinkers (RRR=47.88; 95% CI 35.77 to 64.11), users of mephedrone (RRR=32.38; 95% CI 23.05 to 45.52) and laughing gas users (RRR=3.71; 95% CI 3.04 to 4.51). Multivariate analysis combining demographics and smoking status showed that only gender (being male) and tobacco use independently predicted regular use of e-cigarettes (p<0.001). Among weekly smokers who had tried tobacco and e-cigarettes (n=877), the vast majority reported that they tried tobacco before using an e-cigarette (n=727; 82.9%).

Conclusions

Since 2013, youth experimentation with e-cigarettes has grown rapidly in Wales and is now almost twice as common as experimentation with tobacco. Regular use has almost doubled, and is increasing among never and non-smokers. These data suggest that e-cigarette use among youth is an emerging public health issue, even though there remains no evidence that it represents a new pathway into smoking. Mixed methods longitudinal research is needed to explore why young people use e-cigarettes, and to develop interventions to prevent further increases in use.
Close look at the experiences of patients enrolled in a clinical trial of acupuncture treatment for atrial fibrillation in Korea: a qualitative study nested within a randomised controlled trial
Authors: Lee Seung Min Kathy , Leem Jungtae , Park Jun Hyeong , Yoon Kang Hyun , Woo Jong Shin , Lee Jung Myung , Kim Jin-Bae , Kim Weon , Lee Sanghoon
Published: February 2017

Objective

To explore the experiences of patients with atrial fibrillation (AF) in the context of a prospective, two-parallel-armed, participant-blinded and assessor-blinded sham-controlled randomised trial.

Design

A nested qualitative study within an ongoing randomised controlled trial to explore acupuncture's antiarrhythmic effects on drug refractory acupuncture in persistent atrial fibrillation (AF) (ACU-AF trial).

Participants

Participants were recruited using purposeful sampling and a maximum variation strategy with regard to treatment allocation (treatment or control) and protocol completion (completion or non-completion).

Setting

This was a single-centre in-depth interview qualitative study conducted at a tertiary-level university hospital in Seoul, Republic of Korea.

Results

Data saturation was reached after 8 participants. Thematic analysis identified that most patients were not aware of their condition until medical check-up; physician referral was the main reason for trial participation, and patients had high expectations regardless of previous acupuncture experiences. Patients tended to depend on their physicians' opinions because they felt helpless of their condition. No one questioned their assigned treatment groups and generally believed acupuncture treatment was different for cardiovascular diseases. A few patients expressed disappointment in the strict and rigid protocols, in which most practitioners refrained from explaining their acupuncture procedures.

Conclusions

For cardiovascular patients their physician's advice was one of the biggest reasons for enrolling in the acupuncture trial therefore relying on standard recruitment methods may not be effective. Fortunately both real and sham acupuncture groups in our sample were receiving treatment as intended, but in the future, designing a more pragmatic trial (better reflecting clinical settings, expanding the inclusion criteria and using more treatment points) will allow researchers to better explore the comprehensive effects of acupuncture. The findings of this study will allow researchers to improve the currently ongoing ACU-AF trial and to further help interpretation of main trial outcomes once the trial is completed.

Trial registration number:

NCT02110537.
Regional differences in usage of antenatal care and safe delivery services in Indonesia: findings from a nationally representative survey
Authors: Tripathi Vrijesh , Singh Rajvir
Published: February 2017

Background

Indonesia has shown a nominal increase in antenatal care (ANC) coverage from 93% to 96% in the Indonesia Demographic Health Survey (IDHS)—2012. This is high but for a comprehensive assessment of maternal health coverage in Indonesia, safe delivery services need to be assessed in conjunction with ANC coverage.

Materials and methods

The study uses survey data from the IDHS-2012 that was conducted among women aged 15–49 years who gave birth during the past 3 years preceding the survey. Socioeconomic and demographic factors affecting ANC coverage and safe delivery services are analysed by segregating the data into 7 regions of Indonesia.

Results

Multivariate results show that besides wealth and education differentials, regional differences significantly affect the usage of ANC and safe delivery services across the 7 regions. Univariate analyses show that Sulawesi, Maluku and Western New Guinea islands are at a disadvantage in accessing ANC and safe delivery services.

Conclusions

The study recommends that disaggregated regional targets be set in order to further reduce maternal mortality rates in Indonesia.
Longitudinal study of weight, energy intake and physical activity change across two decades in older Scottish women
Authors: Yang Tiffany C , Gryka Anna A , Aucott Lorna S , Duthie Garry G , Macdonald Helen M
Published: February 2017

Background

The perimenopausal and postmenopausal periods are times of pronounced physiological change in body mass index (BMI), physical activity and energy intake. Understanding these changes in middle age could contribute to formation of potential public health targets.

Method

A longitudinal cohort of 5119 perimenopausal women from the Aberdeen Prospective Osteoporosis Screening Study (APOSS) recruited between 1990 and 1994, with follow-up visits at 1997–1999 and 2009–2011. At each visit, participants were weighed, measured and completed socioeconomic and demographic questionnaires. Participants at the first visit were asked to recall body weights at 20, 30 and 40 years of age. We assessed trends in BMI, physical activity and energy intake across and within visits.

Results

Over 2 decades, obesity prevalence doubled from 14% to 28% of the participants, with 69% of participants being categorised as overweight or obese. Greater than 70% of participants gained >5% of their baseline BMI with weight gain occurring across all weight categories. Energy intake and physical activity levels (PALs) did not change during the 2 decades after menopause (p trend=0.06 and 0.11, respectively), but, within the second visit, energy intake increased concomitantly with a decrease in physical activity across increasing quartiles of BMI (p trend <0.001 for all).

Conclusions

Overweight and obesity increased by over 50% over the course of 20 years. Weight gain occurred across the adult life course regardless of starting weight. The marked increase in dietary intake and decrease in PALs in middle age suggest a potential critical period for intervention to curb excess weight gain.
Elastoplastic consolidation solutions for scaling from shallow penetrometers to pipelines
Authors: Yan Y. , White D.J. , Randolph M.F.
Published: February 2017

The build-up of friction on seabed pipelines is an important design consideration, affecting their stability and the resulting in-service strain and fatigue. The consolidation beneath a partially embedded pipeline has been investigated in the past and linked to the build-up of axial pipe–soil resistance. This paper extends previous work by providing solutions for consolidation around a new class of shallow penetrometer, to provide a basis to scale from site investigation results directly to the build-up of pipeline friction. Small-strain finite element analyses, using the Modified Cam Clay soil model, are presented for the novel toroid and ball penetrometers. The effects of initial penetrometer embedment, device roughness, strength gradient, and overload ratio have been explored in a comprehensive manner, and are compared with pipe results. The toroid penetrometer shows excellent agreement with an element of an infinitely long pipe, simplifying the scaling process. The ball penetrometer shows a faster consolidation response, typically by a factor of three, reflecting the more effective drainage mechanisms of a three-dimensional device compared to a plane strain device. The dissipation responses are fitted by simple equations to aid application in design.
The Knarr Field: a new development at the northern edge of the North Sea
Authors: Skarpeid Silje S. , Churchill James M. , Hilton Jamie P. J. , Izatt Chris N. , Poole Matthew T.
Published: February 2017

The Knarr Field is located in the northern Norwegian North Sea, beyond the Brent Group delta fairway. Knarr was discovered in 2008 with the Jordbær well, additional resources were added to the field in 2011 with the successful Jordbær Vest well. The field extends over an area of approximately 20 km
2
. The original oil in place is estimated to be 26 MSm
3
(163 MBBL). The reservoir is the Late Pliensbachian Cook Formation and its current burial depth is approximately −3700 m true vertical depth subsea (TVDSS). In Knarr, the Cook Formation is split into five sandstones that are separated by four shale intervals which can be correlated across the field. The three lower sands (Lower Cook) are interpreted to have been deposited in a tidally-dominated environment, while the upper two sandstones (Upper Cook) were deposited in a wave-dominated shallow-marine setting. The reservoir properties of the Cook Formation in the Knarr area are remarkably good for a reservoir at this depth, with porosities up to 28% and permeabilities in excess of 1 D. The good reservoir properties are the result of grain-coating chlorite, which has inhibited diagenetic quartz development. The field is developed with three oil producers and three water injectors produced via a floating production storage and offloading vessel (FPSO). First oil was achieved in March 2015.
Break-up and seafloor spreading domains in the NE Atlantic
Authors: Gaina Carmen , Nasuti Aziz , Kimbell Geoffrey S. , Blischke Anett
Published: February 2017

An updated magnetic anomaly grid of the NE Atlantic and an improved database of magnetic anomaly and fracture zone identifications allow the kinematic history of this region to be revisited. At break-up time, continental rupture occurred parallel to the Mesozoic rift axes in the south, but obliquely to the previous rifting trend in the north, probably due to the proximity of the Iceland plume at 57–54 Ma.

The new oceanic lithosphere age grid is based on 30 isochrons (C) from C24n old (53.93 Ma) to C1n old (0.78 Ma), and documents ridge reorganizations in the SE Lofoten Basin, the Jan Mayen Fracture Zone region, in Iceland and offshore Faroe Islands. Updated continent–ocean boundaries, including the Jan Mayen microcontinent, and detailed kinematics of the Eocene–Present Greenland–Eurasia relative motions are included in this model.

Variations in the subduction regime in the NE Pacific could have caused the sudden northwards motion of Greenland and subsequent Eurekan deformation. These events caused seafloor spreading changes in the neighbouring Labrador Sea and a decrease in spreading rates in the NE Atlantic. Boundaries between major oceanic crustal domains were formed when the European Plate changed its absolute motion direction, probably caused by successive adjustments along its southern boundary.

Supplementary material:
Figures showing the long wavelength of the NAG-TEC magnetic anomaly grid, detailed magnetic anomalies and isochrons, and a Table documenting aeromagnetic surveys for NAG-TEC magnetic compilation are available at
https://doi.org/10.6084/m9.figshare.c.3661925
Cardiac Med1 deletion promotes early lethality, cardiac remodeling, and transcriptional reprogramming
Authors: Spitler Kathryn M. , Ponce Jessica M. , Oudit Gavin Y. , Hall Duane D. , Grueter Chad E.
Published: February 2017

The mediator complex, a multisubunit nuclear complex, plays an integral role in regulating gene expression by acting as a bridge between transcription factors and RNA polymerase II. Genetic deletion of mediator subunit 1 (Med1) results in embryonic lethality, due in large part to impaired cardiac development. We first established that Med1 is dynamically expressed in cardiac development and disease, with marked upregulation of Med1 in both human and murine failing hearts. To determine if Med1 deficiency protects against cardiac stress, we generated two cardiac-specific Med1 knockout mouse models in which Med1 is conditionally deleted (Med1cKO mice) or inducibly deleted in adult mice (Med1cKO-MCM mice). In both models, cardiac deletion of Med1 resulted in early lethality accompanied by pronounced changes in cardiac function, including left ventricular dilation, decreased ejection fraction, and pathological structural remodeling. We next defined how Med1 deficiency alters the cardiac transcriptional profile using RNA-sequencing analysis. Med1cKO mice demonstrated significant dysregulation of genes related to cardiac metabolism, in particular genes that are coordinated by the transcription factors Pgc1α, Pparα, and Errα. Consistent with the roles of these transcription factors in regulation of mitochondrial genes, we observed significant alterations in mitochondrial size, mitochondrial gene expression, complex activity, and electron transport chain expression under Med1 deficiency. Taken together, these data identify Med1 as an important regulator of vital cardiac gene expression and maintenance of normal heart function.

NEW & NOTEWORTHY Disruption of transcriptional gene expression is a hallmark of dilated cardiomyopathy; however, its etiology is not well understood. Cardiac-specific deletion of the transcriptional coactivator mediator subunit 1 (Med1) results in dilated cardiomyopathy, decreased cardiac function, and lethality. Med1 deletion disrupted cardiac mitochondrial and metabolic gene expression patterns.
Transcriptomic alterations in the brain of painted turtles (Chrysemys picta) developmentally exposed to bisphenol A or ethinyl estradiol
Authors: Manshack Lindsey K. , Conard Caroline M. , Bryan Sara J. , Deem Sharon L. , Holliday Dawn K. , Bivens Nathan J. , Givan Scott A. , Rosenfeld Cheryl S.
Published: February 2017

Developmental exposure of turtles and other reptiles to endocrine-disrupting chemicals (EDCs), including bisphenol A (BPA) and ethinyl estradiol (EE), can stimulate partial to full gonadal sex-reversal in males. We have also recently shown that in ovo exposure to either EDC can induce similar sex-dependent behavioral changes typified by improved spatial learning and memory or possibly feminized brain responses. Observed behavioral changes are presumed to be due to BPA- and EE-induced brain transcriptomic alterations during development. To test this hypothesis, we treated painted turtles ( Chrysemys picta) at developmental stage 17, incubated at 26°C (male-inducing temperature), with 1) BPA (1 ng/µl), 2) EE (4 ng/µl), or 3) vehicle ethanol (control group). Ten months after hatching and completion of the behavioral tests, juvenile turtles were euthanized, brains were collected and frozen in liquid nitrogen, and RNA was isolated for RNA-Seq analysis. Turtles exposed to BPA clustered separately from EE-exposed and control individuals. More transcripts and gene pathways were altered in BPA vs. EE individuals. The one transcript upregulated in both BPA- and EE-exposed individuals was the mitochondrial-associated gene, ND5, which is involved in oxidative phosphorylation. Early exposure of turtles to BPA increases transcripts linked with ribosomal and mitochondrial functions, especially bioenergetics, which has been previously linked with improved cognitive performance. In summary, even though both BPA and EE resulted in similar behavioral alterations, they diverge in the pattern of neural transcript alterations with early BPA significantly upregulating several genes involved in oxidative phosphorylation, mitochondrial activity, and ribosomal function, which could enhance cognitive performance.
Intrinsic Resistance of Solid Tumors to Immune Checkpoint Blockade Therapy
Authors: Zhao Xianda , Subramanian Subbaya
Published: February 2017

Immune checkpoint blockade therapy (ICBT), which blocks negative immune-activating signals and maintains the antitumor response, has elicited a remarkable clinical response in certain cancer patients. However, intrinsic resistance (i.e., insensitivity of the tumors to therapy) remains a daunting challenge. The efficacy of ICBT is tightly modulated by the function of each step in the antitumor immunity cycle. Mechanistically, the number of mutations determines tumor immunogenicity. The properties of the tumor microenvironment control T-cell infiltration, distribution, and function in tumor tissues. Low tumor immunogenicity and a strong immunosuppressive tumor microenvironment cause significant intrinsic resistance to ICBT. With our evolving understanding of intrinsic resistance, people have successfully tested, in preclinical models, treatments targeting specific resistance mechanisms to sensitize ICBT-resistant tumors. Translation of those preclinical findings to the clinical arena will help generate personalized ICBT strategies that target tumor-specific resistance mechanisms. Progress in the new personalized ICBT strategies will expand the reach of immunotherapy to more cancer types, thus enabling more patients to benefit. Cancer Res; 77(4); 817–22. ©2017 AACR.
Estradiol Promotes Breast Cancer Cell Migration via Recruitment and Activation of Neutrophils
Authors: Vazquez Rodriguez Gabriela , Abrahamsson Annelie , Jensen Lasse Dahl Ejby , Dabrosin Charlotta
Published: February 2017

Estradiol (E2) plays a key role in breast cancer progression. Most breast cancer recurrences express the estrogen receptor (ER), but nearly 50% of patients are resistant to antiestrogen therapy. Novel therapeutic targets of ER-positive breast cancers are needed. Protumoral neutrophils expressing the lymphocyte function-associated antigen 1 (LFA-1) integrin may mediate cancer metastasis, and TGFβ1 is the major chemoattractant for neutrophils. The role of E2 in neutrophil–ER+ breast cancer cell interactions is unknown. We studied this in vivo using murine breast cancers in immunocompetent mice and human breast cancers in nude mice. Cell dissemination was evaluated in a zebrafish model, and microdialysis of breast cancer patients was performed. In vitro studies were done with mammosphere cultures of breast cancer cells and human neutrophils. We found that E2 increased the number of LFA-1+ neutrophils recruited to the invasive edge of mouse tumors, increased TGFβ1 secretion and promoted neutrophil infiltration in mammospheres, and induced overexpression of LFA-1 in neutrophils. In zebrafish, in the presence of E2, neutrophils increased dissemination of ER+ breast cancer cells via LFA-1 and TGFβ1, thus causing noninvasive cancer cells to be highly metastatic. Time-lapse imaging in zebrafish revealed close interactions of neutrophils with cancer cells, which drove breast cancer metastasis. We also found that extracellular TGFβ1 was overproduced in human breast cancer tissue compared with adjacent normal breast tissue. Thus, E2 can regulate immune/cancer cell interactions in tumor microenvironments. Our results indicate that extracellular TGFβ1 is a relevant target in human breast cancer. Cancer Immunol Res; 5(3); 234–47. ©2017 AACR.
NK-Cell Recruitment Is Necessary for Eradication of Peritoneal Carcinomatosis with an IL12-Expressing Maraba Virus Cellular Vaccine
Authors: Alkayyal Almohanad A. , Tai Lee-Hwa , Kennedy Michael A. , de Souza Christiano Tanese , Zhang Jiqing , Lefebvre Charles , Sahi Shalini , Ananth Abhirami A. , Mahmoud Ahmad Bakur , Makrigiannis Andrew P. , Cron Greg O. , Macdonald Blair , Marginean E. Celia , Stojdl David F. , Bell John C. , Auer Rebecca C.
Published: February 2017

Despite improvements in chemotherapy and radical surgical debulking, peritoneal carcinomatosis (PC) remains among the most common causes of death from abdominal cancers. Immunotherapies have been effective for selected solid malignancies, but their potential in PC has been little explored. Here, we report that intraperitoneal injection of an infected cell vaccine (ICV), consisting of autologous tumor cells infected ex vivo with an oncolytic Maraba MG1 virus expressing IL12, promotes the migration of activated natural killer (NK) cells to the peritoneal cavity in response to the secretion of IFNγ-induced protein-10 (IP-10) from dendritic cells. The recruitment of cytotoxic, IFNγ-secreting NK cells was associated with reduced tumor burden and improved survival in a colon cancer model of PC. Even in mice with bulky PC (tumors > 8 mm), a complete radiologic response was demonstrated within 8 to14 weeks, associated with 100% long-term survival. The impact of MG1-IL12-ICV upon NK-cell recruitment and function observed in the murine system was recapitulated in human lymphocytes exposed to human tumor cell lines infected with MG1-IL12. These findings suggest that an MG1-IL12-ICV is a promising therapy that could provide benefit to the thousands of patients diagnosed with PC each year. Cancer Immunol Res; 5(3); 211–21. ©2017 AACR.
Serum Chloride and Sodium Interplay in Patients With Acute Myocardial Infarction and Heart Failure With Reduced Ejection Fraction
Authors: Ferreira João Pedro , Girerd Nicolas , Duarte Kevin , Coiro Stefano , McMurray John J. V. , Dargie Henry J. , Pitt Bertram , Dickstein Kenneth , Testani Jeffrey M. , Zannad Faiez , Rossignol Patrick
Published: February 2017

Background—

Serum chloride levels were recently found to be independently associated with mortality in heart failure (HF).

Methods and Results—

We investigated the relationship between serum chloride and clinical outcomes in 7195 subjects with acute myocardial infarction complicated by reduced left ventricular function and HF. The studied outcomes were all-cause mortality, cardiovascular mortality, and hospitalization for HF. Both chloride and sodium had a nonlinear association with the studied outcomes (
P
<0.05 for linearity). Patients in the lowest chloride tertile (chloride ≤100) were older, had more comorbidities, and had lower sodium levels (
P
<0.05 for all). Serum chloride showed a significant interaction with sodium with regard to all studied outcomes (
P
for interaction <0.05 for all). The lowest chloride tertile (≤100 mmol/L) was associated with increased mortality rates in the context of lower sodium (≤138 mmol/L; adjusted hazard ratio [95% confidence interval] for all-cause mortality=1.42 (1.14–1.77);
P
=0.002), whereas in the context of higher sodium levels (>141 mmol/L), the association with mortality was lost. Spline-transformed chloride and its interaction with sodium did not add significant prognostic information on top of other well-established prognostic variables (
P
>0.05 for all outcomes).

Conclusions—

In post–myocardial infarction with systolic dysfunction and HF, low serum chloride was associated with mortality (but not hospitalization for HF) in the setting of lower sodium. Overall, chloride and its interaction with sodium did not add clinically relevant prognostic information on top of other well-established prognostic variables. Taken together, these data support an integrated and critical consideration of chloride and sodium interplay.