bluuebunny/crossref_metadata_2025 huggingface dataset:
PhoU2 but Not PhoU1 as an Important Regulator of Biofilm Formation and Tolerance to Multiple Stresses by Participating in Various Fundamental Metabolic Processes in Staphylococcus epidermidis
Authors: Wang Xiaofei , Han Haiyan , Lv Zhihui , Lin Zhiwei , Shang Yongpeng , Xu Tao , Wu Yang , Zhang Ying , Qu Di
Published: September 2017

PhoU, a conserved protein that has been proposed to coordinate phosphate import, is a negative regulator of drug tolerance in most bacteria. In
Staphylococcus epidermidis
, the role of PhoU in biofilm formation and drug tolerance has not yet been investigated. Two PhoU homologs in the genome of
S. epidermidis
have been identified by the presence of the conserved motif E(D)XXXD of PhoU. We separately constructed Δ
phoU1
and Δ
phoU2
mutants of
S. epidermidis
strain 1457. The Δ
phoU2
mutant displayed growth retardation, a weakened biofilm formation capacity, a higher sensitivity to H
2
O
2
, and reduced tolerance to multiple antibiotics. However, deletion of
phoU1
had no effect on those. We compared the transcriptome profiles of the Δ
phoU2
and Δ
phoU1
mutants with that of the parent strain. In the Δ
phoU2
mutant, expression of genes related to inorganic phosphate uptake was significantly upregulated (
pst
operon) and the levels of intracellular inorganic polyphosphate (polyP) were increased. In the Δ
phoU2
mutant, expression of enzymes in the pentose phosphate pathway (PPP) was downregulated and less NADP (NADPH) was detected, consistent with the high sensitivity to H
2
O
2
and the growth retardation of the Δ
phoU2
mutant. The upregulated expression of ATP synthase was consistent with the high intracellular ATP content in the Δ
phoU2
mutant, which may have been related to the lower drug tolerance of the Δ
phoU2
mutant. This study demonstrates that PhoU2, but not PhoU1, in
S. epidermidis
regulates bacterial growth, biofilm formation, oxidative stress, and drug tolerance in association with alterations to inorganic phosphate metabolism, the pentose phosphate pathway, galactose metabolism, the tricarboxylic acid (TCA) or citric cycle, glycolysis and gluconeogenesis, and respiratory reactions.

IMPORTANCE
PhoU is widely conserved throughout the bacterial kingdom and plays an important role in response to stress and metabolic maintenance. In our study, two PhoU homologs were found in
S. epidermidis
. The function of
phoU2
, but not
phoU1
, in
S. epidermidis
is related to growth, drug tolerance, the oxidative stress response, polyP levels, and ATP accumulation. In addition,
phoU2
regulates biofilm formation. Hence,
phoU2
is a regulator of both drug tolerance and biofilm formation, which are two bacterial properties that present major challenges to the clinical treatment of infections. Analysis of differential gene expression revealed that
phoU2
is involved in fundamental metabolic processes, such as the PPP pathway. These findings indicate that
phoU2
is a crucial regulator in
S. epidermidis
.
Phenotypes of

dnaX
E145A

Mutant Cells Indicate that the Escherichia coli Clamp Loader Has a Role in the Restart of Stalled Replication Forks
Authors: Flåtten Ingvild , Helgesen Emily , Pedersen Ida Benedikte , Waldminghaus Torsten , Rothe Christiane , Taipale Riikka , Johnsen Line , Skarstad Kirsten
Published: September 2017

The
Escherichia coli

dnaX
E145A

mutation was discovered in connection with a screen for multicopy suppressors of the temperature-sensitive topoisomerase IV mutation
parE10
. The gene for the clamp loader subunits τ and γ,
dnaX
, but not the mutant

dnaX
E145A

, was found to suppress
parE10
(Ts) when overexpressed. Purified mutant protein was found to be functional
in vitro
, and few phenotypes were found
in vivo
apart from problems with partitioning of DNA in rich medium. We show here that a large number of the replication forks that initiate at
oriC
never reach the terminus in

dnaX
E145A

mutant cells. The SOS response was found to be induced, and a combination of the

dnaX
E145A

mutation with
recBC
and
recA
mutations led to reduced viability. The mutant cells exhibited extensive chromosome fragmentation and degradation upon inactivation of
recBC
and
recA
, respectively. The results indicate that the

dnaX
E145A

mutant cells suffer from broken replication forks and that these need to be repaired by homologous recombination. We suggest that the
dnaX
-encoded τ and γ subunits of the clamp loader, or the clamp loader complex itself, has a role in the restart of stalled replication forks without extensive homologous recombination.

IMPORTANCE
The
E. coli
clamp loader complex has a role in coordinating the activity of the replisome at the replication fork and loading β-clamps for lagging-strand synthesis. Replication forks frequently encounter obstacles, such as template lesions, secondary structures, and tightly bound protein complexes, which will lead to fork stalling. Some pathways of fork restart have been characterized, but much is still unknown about the actors and mechanisms involved. We have in this work characterized the

dnaX
E145A

clamp loader mutant. We find that the naturally occurring obstacles encountered by a replication fork are not tackled in a proper way by the mutant clamp loader and suggest a role for the clamp loader in the restart of stalled replication forks.
Rolling Circle Mutagenesis of GST-mCherry to Understand Mutation, Gene Expression, and Regulation
Authors: Cole Jessica , Ferguson Amanda , Segarra Verónica A. , Walsh Susan
Published: September 2017

Undergraduates are often familiar with textbook examples of human mutations that affect coding regions and the subsequent disorders, but they may struggle with understanding the implications of mutations in the regulatory regions of genes. We have designed a laboratory sequence that will allow students to explore the effect random mutagenesis can have on protein function, expression, and ultimately phenotype. Students design and perform a safe and time-efficient random mutagenesis experiment using error-prone rolling circular amplification of a plasmid expressing the inducible fusion protein glutathione S-transferase (GST)-mCherry. Mutagenized and wild-type control plasmid DNA, respectively, are then purified and transformed into bacteria to assess phenotypic changes. While bacteria transformed with the wild type control should be pink, some bacterial colonies transformed with mutagenized plasmids will exhibit a different color. Students attempt to identify their mutations by isolating plasmid from these mutant colonies, sequencing, and comparing their mutant sequence to the wild-type sequence. Additionally, students evaluate the potential effects of mutations on protein production by inducing GST-mCherry expression in cultures, generating cell lysates, and analyzing them using SDS-PAGE. Students who have a phenotypic difference but do not obtain a coding region mutation will be able to think critically about plasmid structure and regulation outside of the gene sequence. Students who do not obtain bacterial transformants have the chance to contemplate how mutation of antibiotic resistance genes or replication origins may have contributed to their results. Overall, this series of laboratories exposes students to basic genetic techniques and helps them conceptualize mutation beyond coding regions.
Laboratory Activity to Promote Student Understanding of UV Mutagenesis and DNA Repair
Authors: Kouassi Joshua Ernest , Waldron Ingrid , Tripepi Manuela , Pohlschroder Mechthild
Published: September 2017

Changes in DNA molecules are common, due to the effects of UV light and other external and internal mutagens. Cells have a variety of repair mechanisms which serve to maintain the accuracy of the genetic code. This activity includes a low-cost, safe and technically feasible experiment, which allows students to observe the effects of UV mutagenesis and DNA photorepair in the halophilc archaeon, Haloferax volcanii. An optional extension links this activity to topics of immediate concern to students – how exposure to UVC light contributes to skin cancer risk and the protective effects of sunscreen. Students design and carry out an experiment to test whether SPF 15 sunscreen increases the lethal exposure time for H. volcanii by a factor of 15. Throughout the activity, discussion questions engage students in actively thinking about the biological phenomena and experimental procedures and analysis.

This activity is designed for students in college or university genetics, microbiology, or introductory biology courses as well as in high school honors biology courses. Teachers report that this activity was valuable in helping students understand mutagenesis and photorepair and in developing student skills in designing and analyzing experiments.
Method to Increase Undergraduate Laboratory Student Confidence in Performing Independent Research
Authors: Kempton Colton E. , Weber K. Scott , Johnson Steven M.
Published: September 2017

The goal of an undergraduate laboratory course should be not only to introduce the students to biology methodologies and techniques, but also to teach them independent analytical thinking skills and proper experiment design. This is especially true for advanced biology laboratory courses that undergraduate students typically take as a junior or senior in college. Many courses achieve the goal of teaching techniques, but fail to approach the larger goal of teaching critical thinking, experimental design, and student independence. Here we describe a study examining the application of the scaffolding instructional philosophy in which students are taught molecular techniques with decreasing guidance to force the development of analytical thinking skills and prepare undergraduate students for independent laboratory research. This method was applied to our advanced molecular biology laboratory class and resulted in an increase of confidence among the undergraduate students in their abilities to perform independent research.
Unique Down to Our Microbes—Assessment of an Inquiry-Based Metagenomics Activity
Authors: Lentz Thomas B. , Ott Laura E. , Robertson Sabrina D. , Windsor Sarah C. , Kelley Joshua B. , Wollenberg Michael S. , Dunn Robert R. , Goller Carlos C.
Published: September 2017

Metagenomics is an important method for studying microbial life. However, undergraduate exposure to metagenomics is hindered by associated software, computing demands, and dataset access. In this inquiry-based activity designed for introductory life science majors and nonmajors, students perform an investigation of the bacterial communities inhabiting the human belly button and associated metagenomics data collected through a citizen science project and visualized using an open-access bioinformatics tool. The activity is designed for attainment of the following student learning outcomes: defining terms associated with metagenomics analyses, describing the biological impact of the microbiota on human health, formulating a hypothesis, analyzing and interpreting metagenomics data to compare microbiota, evaluating a specific hypothesis, and synthesizing a conceptual model as to why bacterial populations vary. This activity was implemented in six introductory biology and biotechnology courses across five institutions. Attainment of student learning outcomes was assessed through completion of a quiz and students’ presentations of their findings. In presentations, students demonstrated their ability to develop novel hypotheses and analyze and interpret metagenomic data to evaluate their hypothesis. In quizzes, students demonstrated their ability to define key terms and describe the biological impact of the microbiota on human health. Student learning gains assessment also revealed that students perceived gains for all student learning outcomes. Collectively, our assessment demonstrates achievement of the learning outcomes and supports the utility of this inquiry-based activity to engage undergraduates in the scientific process via analyses of metagenomics datasets and associated exploration of a microbial community that lives on the human body.
Artificial Urine for Teaching Urinalysis Concepts and Diagnosis of Urinary Tract Infection in the Medical Microbiology Laboratory
Authors: Khan Latifa B. , Read Hannah M. , Ritchie Stephen R. , Proft Thomas
Published: September 2017

Dipstick urinalysis is an informative, quick, cost-effective and non-invasive diagnostic tool that is useful in clinical practice for the diagnosis of urinary tract infections (UTIs), kidney diseases, and diabetes. We used dipstick urinalysis as a hands-on microbiology laboratory exercise to reinforce student learning about UTIs with a particular focus on cystitis, which is a common bacterial infection. To avoid exposure to potentially contaminated human urine samples, we prepared artificial urine using easily acquired and affordable ingredients, which allowed less-experienced students to perform urinalysis without the risk of exposure to pathogenic organisms and ensured reliable availability of the urine samples. This practical class taught medical students how to use urinalysis data in conjunction with medical history to diagnose diseases from urine samples and to determine a treatment plan for clinical scenarios.
Education is the Only Business Where the Customer is Satisfied with Less of the Product
Authors: Klionsky Daniel J.
Published: September 2017

Faculty members need to be vigilant to avoid a slide toward decreased efforts in the classroom. The demand for “good teaching” may not come from the students in the class, who have many activities taking up their time and are often satisfied with a course that makes minimal demands; however, even tenured faculty members should strive for higher standards, including maintaining high expectations of the students. One of the seven principles for good practice in undergraduate education, as espoused by Chickering and Gamson, is “communicates high expectations” (1); that is, students tend to put in the effort necessary to meet expectations, so it makes sense to set a high bar for performance, even though it may take extra work on the part of the instructor.
Young girl with severe early-onset obesity and hyperphagia
Authors: Kleinendorst Lotte , van Haelst Mieke M , van den Akker Erica L T
Published: September 2017

This case report of an infant with severe early-onset obesity illustrates the societal condemnation of persons with obesity. In addition, it underlines the importance of diagnosing rare forms of monogenic obesity, even if no drug treatment is available. Here, we describe a 2-year-old girl with severe progressive obesity from birth onwards due to insatiable hunger. Genetic studies eventually reveal that the girl has a monogenic form of obesity caused by two mutations in theLEPRgene. No drug treatment is available (as yet) for this disease. Parents describe the stigmatic remarks they have to deal with every day. Diagnosing this rare genetic disorder was very important for understanding that satiety regulation is a complex system, of which willpower is only a small portion. In these patients, reduction of obesity can be achieved, but a different approach to lifestyle intervention is needed.
Population-based cohort study examining the association between splenectomy and empyema in adults in Taiwan
Authors: Lin Hsien-Feng , Liao Kuan-Fu , Chang Ching-Mei , Lin Cheng-Li , Lai Shih-Wei
Published: September 2017

Objective

This study aimed to investigate the association between splenectomy and empyema in Taiwan.

Methods

A population-based cohort study was conducted using the hospitalisation dataset of the Taiwan National Health Insurance Program. A total of 13 193 subjects aged 20–84 years who were newly diagnosed with splenectomy from 2000 to 2010 were enrolled in the splenectomy group and 52 464 randomly selected subjects without splenectomy were enrolled in the non-splenectomy group. Both groups were matched by sex, age, comorbidities and the index year of undergoing splenectomy. The incidence of empyema at the end of 2011 was calculated. A multivariable Cox proportional hazards regression model was used to estimate the HR with 95% CI of empyema associated with splenectomy and other comorbidities.

Results

The overall incidence rate of empyema was 2.56-fold higher in the splenectomy group than in the non-splenectomy group (8.85 vs 3.46 per 1000 person-years). The Kaplan-Meier analysis revealed a higher cumulative incidence of empyema in the splenectomy group than in the non-splenectomy group (6.99% vs 3.37% at the end of follow-up). After adjusting for confounding variables, the adjusted HR of empyema was 2.89 for the splenectomy group compared with that for the non-splenectomy group. Further analysis revealed that HR of empyema was 4.52 for subjects with splenectomy alone.

Conclusion

The incidence rate ratio between the splenectomy and non-splenectomy groups reduced from 2.87 in the first 5 years of follow-up to 1.73 in the period following the 5 years. Future studies are required to confirm whether a longer follow-up period would further reduce this average ratio. For the splenectomy group, the overall HR of developing empyema was 2.89 after adjusting for age, sex and comorbidities, which was identified from previous literature. The risk of empyema following splenectomy remains high despite the absence of these comorbidities.
Relationship of altitude mountain sickness and smoking: a Catalan traveller’s cohort study
Authors: Sánchez-Mascuñano Alba , Masuet-Aumatell Cristina , Morchón-Ramos Sergio , Ramon Josep M
Published: September 2017

Objectives

The aim of this study is to analyse the relationship between smoking andaltitude mountain sicknessin a cohort of travellers to 2500 metres above sea level (masl) or higher.

Setting

Travel Health Clinic at the Hospital Universitari de Bellvitge, in Barcelona, Spain.

Participants

A total of 302 adults seeking medical advice at the travel clinic, between July 2012 and August 2014, before travelling to 2500 masl or above, who agreed to participate in the study and to be contacted after the trip were included. Individuals who met the following criteria were excluded: younger than 18 years old, taking carbonic anhydrase inhibitors for chronic use, undergoing treatment with systemic corticosteroids and taking any medication that might prevent or treat altitude mountain sickness (AMS) prior to or during the trip. The majority of participants were women (n=156, 51.7%). The mean age was 37.7 years (SD 12.3). The studied cohort included 74 smokers (24.5%), 158 (52.3%) non-smokers and 70 (23.2%) ex-smokers. No statistical differences were observed between different sociodemographic characteristics, constitutional symptoms or drug use and smoking status.

Outcomes

The main outcome was the development of AMS, which was defined according to the Lake Louise AMS criteria.

Results

AMS, according to the Lake Louise score, was significantly lower in smokers; the value was 14.9%, 95% CI (6.8 to 23.0%) in smokers and 29.4%, 95% CI (23.5 to 35.3%) in non-smokers with an adjusted OR of 0.54, 95% CI (0.31 to 0.97) independent of gender, age and maximum altitude reached.

Conclusions

These results suggest that smoking could reduce the risk of AMS in non-acclimated individuals. Further studies should be performed in larger cohorts of travellers to confirm these results. Despite the results, smoking must be strongly discouraged because it greatly increases the risk of cardiorespiratory diseases, cancer and other diseases.
Baseline characteristics, survival and direct costs associated to treatment of gastric cancer patients at the National Oncology Institute of Panama from 2012 to 2015: a hospital-based observational study
Authors: Castro Franz , Shahal David , Tarajia Musharaf , Velásquez Ilais Moreno , Causadias Maribel Tribaldos , Herrera Víctor , Gómez Beatriz , Cukier Moisés , Motta Jorge
Published: September 2017

Objectives

Comprehensive epidemiological and economic studies of gastric cancer (GC) in Panama are limited. This study aims to evaluate the association between socioeconomic and clinical variables with survival, describe the survival outcomes according to clinical stage and estimate the direct costs associated to GC care in a Panamanian population with GC.

Design and setting

A retrospective observational study was conducted at the leading public institution for cancer treatment in Panama.

Participants

Data were obtained from 611 records of patients diagnosed with gastric adenocarcinoma (codes C16.0–C16.9 of the International Classification of Diseases 10th revision), identified between 1 January 2012 and 31 December 2015.

Methods

Cox proportional hazards models were used to calculate HRs with 95%  CI to examine associations between the variables and survival. Kaplan-Meier curves were used to assess overall and stage-specific survival. Direct costs (based on 2015 US$) were calculated per patient using standard costs provided by the institution for hospital admission (occupied bed-days), radiotherapy, surgery and chemotherapy, yielding total and overall mean costs (OMC). A comparison of OMC between groups (sex, social security status, clinical stage) was performed applying the bootstrap method with a t-test of unequal variances.

Results

An increased risk of dying was observed for patients without social security coverage (HR: 2.02; 95% CI 1.16 to 3.53), overlapping tumours (HR: 1.50; 95% CI 1.02 to 2.22), poorly differentiated tumours (HR: 2.27; 95% CI 1.22 to 4.22) and stage IV disease (HR: 5.54; 95% CI 3.38 to 9.08) (adjusted models). Overall 1-year survival rate was 41%. The estimated OMC of GC care per patient was 4259 US$. No statistically significant differences were found in OMC between groups.

Conclusions

Socioeconomic disparities influence GC outcomes and healthcare utilisation. Policies addressing healthcare disparities related to GC are needed, as well as in-depth studies evaluating barriers of access to GC-related services.
Participant acceptability of exercise in kidney disease (PACE-KD): a feasibility study protocol in renal transplant recipients
Authors: Bishop Nicolette C , Billany Roseanne , Smith Alice C
Published: September 2017

Introduction

Cardiovascular disease (CVD) is a major cause of mortality in renal transplant recipients (RTRs). General population risk scores for CVD underestimate the risk in patients with chronic kidney disease (CKD) suggesting additional non-traditional factors. Renal transplant recipients also exhibit elevated inflammation and impaired immune function. Exercise has a positive impact on these factors in patients with CKD but there is a lack of rigorous research in RTRs, particularly surrounding the feasibility and acceptability of high-intensity interval training (HIIT) versus moderate-intensity continuous training (MICT) in this population. This study aims to explore the feasibility of three different supervised aerobic exercise programmes in RTRs to guide the design of future large-scale efficacy studies.

Methods and analysis

Renal transplant recipients will be randomised to HIIT A (16 min interval training with 4, 2 and 1 min intervals at 80%–90% of peak oxygen uptake (VO2 peak)), HIIT B (4×4 min interval training at 80%–90% VO2peak) or MICT (~40 min cycling at 50%–60% VO2peak) where they will undertake 24 supervised sessions (approximately thrice weekly over 8 weeks). Assessment visits will be at baseline, midtraining, immediate post-training and 3 months post-training. The study will evaluate the feasibility of recruitment, randomisation, retention, assessment procedures and the implementation of the interventions. A further qualitative sub-study QPACE-KD (Qualitative Participant Acceptability of Exercise in Kidney Disease) will explore patient experiences and perspectives through semistructured interviews and focus groups.

Ethics and dissemination

All required ethical and regulatory approvals have been obtained. Findings will be disseminated through conference presentations, public platforms and academic publications.

Trial registration number

Prospectively registered;ISRCTN17122775.
Maternal ambient air pollution, preterm birth and markers of fetal growth in Rhode Island: results of a hospital-based linkage study
Authors: Kingsley Samantha L , Eliot Melissa N , Glazer Kimberly , Awad Yara Abu , Schwartz Joel D , Savitz David A , Kelsey Karl T , Marsit Carmen J , Wellenius Gregory A
Published: September 2017

Background

Maternal exposure to ambient air pollution has been associated with higher risk of preterm birth and reduced fetal growth, but heterogeneity among prior studies suggests that additional studies are needed in diverse populations and settings. We examined the associations between maternal ambient air pollution levels, risk of preterm birth and markers of fetal growth in an urban population with relatively low exposure to air pollution.

Methods

We linked 61 640 mother–infant pairs who delivered at a single hospital in Providence, Rhode Island, from 2002 to 2012 to birth certificate and hospital discharge data. We used spatial-temporal models and stationary monitors to estimate exposure to fine particulate matter (PM2.5) and black carbon (BC) during pregnancy. Using generalised linear models, we evaluated the association between pollutant levels, risk of preterm birth and markers of fetal growth.

Results

In adjusted models, an IQR (2.5 µg/m3) increase in pregnancy-average PM2.5was associated with ORs of preterm birth of 1.04 (95% CI 0.94 to 1.15) and 0.86 (0.76 to 0.98) when considering modelled and monitored PM2.5, respectively. An IQR increase in modelled and monitored PM2.5was associated with a 12.1 g (95% CI −24.2 to –0.1) and 15.9 g (95% CI −31.6 to –0.3) lower birth weight. Results for BC were highly sensitive to choice of exposure metric.

Conclusion

In a population with relatively low exposures to ambient air pollutants, PM2.5was associated with reduced birth weight but not with risk of preterm birth.
Influence of Dietary Macronutrients on Liver Fat Accumulation and Metabolism
Authors: Parry Siôn A , Hodson Leanne
Published: September 2017

The liver is a principal metabolic organ within the human body and has a major role in regulating carbohydrate, fat, and protein metabolism. With increasing rates of obesity, the prevalence of non-alcoholic fatty liver disease (NAFLD) is growing. It remains unclear why NAFLD, which is now defined as the hepatic manifestation of the metabolic syndrome, develops but lifestyle factors such as diet (ie, total calorie and specific nutrient intakes), appear to play a key role. Here we review the available observational and intervention studies that have investigated the influence of dietary macronutrients on liver fat content. Findings from observational studies are conflicting with some reporting that relative to healthy controls, patients with NAFLD consume diets higher in total fat/saturated fatty acids, whilst others find they consume diets higher in carbohydrates/sugars. From the limited number of intervention studies that have been undertaken, a consistent finding is a hypercaloric diet, regardless of whether the excess calories have been provided either as fat, sugar, or both, increases liver fat content. In contrast, a hypocaloric diet decreases liver fat content. Findings from both hyper- and hypo-caloric feeding studies provide some suggestion that macronutrient composition may also play a role in regulating liver fat content and this is supported by data from isocaloric feeding studies; fatty acid composition and/or carbohydrate content/type appear to influence whether there is accrual of liver fat or not. The mechanisms by which specific macronutrients, when consumed as part of an isocaloric diet, cause a change in liver fat remain to be fully elucidated.
Estrogenic Potentials of Traditional Chinese Medicine
Authors: Kiyama Ryoiti
Published: September 2017

Estrogen, a steroid hormone, is associated with several human activities, including environmental, industrial, agricultural, pharmaceutical and medical fields. In this review paper, estrogenic activity associated with traditional Chinese medicines (TCMs) is discussed first by focusing on the assays needed to detect estrogenic activity (animal test, cell assay, ligand-binding assay, protein assay, reporter-gene assay, transcription assay and yeast two-hybrid assay), and then, their sources, the nature of activities (estrogenic or anti-estrogenic, or other types), and pathways/functions, along with the assay used to detect the activity, which is followed by a summary of effective chemicals found in or associated with TCM. Applications of estrogens in TCM are then discussed by a comprehensive search of the literature, which include basic study/pathway analysis, cell functions, diseases/symptoms and medicine/supplements. Discrepancies and conflicting cases about estrogenicity of TCM among assays or between TCM and their effective chemicals, are focused on to enlarge estrogenic potentials of TCM by referring to omic knowledge such as transcriptome, proteome, glycome, chemome, cellome, ligandome, interactome and effectome.
Geochronology, geochemistry and isotope systematics of a mafic–intermediate dyke complex in the İstanbul Zone. New constraints on the evolution of the Black Sea in NW Turkey
Authors: Aysal Namık , Keskin Mehmet , Peytcheva Irena , Duru Olgun
Published: September 2017

We report new U–Pb zircon ages, major and trace element data, mineral chemistry, and Sr–Nd isotopic analyses of the mafic–intermediate dykes and intrusions in the İstanbul Zone. Mafic dykes are represented by calc-alkaline to alkaline lamprophyre and diabase. Intermediate dykes and subvolcanics are andesitic to dacitic in composition and calc-alkaline in character, while intrusive rocks (stocks and small plutons) are granodioritic and dioritic in composition. New zircon U–Pb laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) dating yielded ages from 72.49 ± 0.79 (Upper Cretaceous–Campanian) to 65.44 ± 0.93 Ma (Lower Paleocene–Danian) for the intermediate dykes, and 58.9 ± 1.8 Ma (Upper Paleocene–Thanetian) for a small granodiorite stock.
87
Sr/
86
Sr
(i)
values of the mafic and intermediate dykes and small stocks span a range from 0.703508 to 0.706311, while their
143
Nd/
144
Nd
(i)
values vary from 0.512614 to 0.512812 and eNd
(i)
values from 5.09 to 1.24. Nd
TDM
model ages range between 0.46 and 0.77 Ga.

Dykes are enriched in large ion lithophile elements (LILEs) and light rare earth elements (LREEs) relative to high field strength elements (HFSEs). Normal-type mid-ocean ridge basalt (N-MORB)-normalized multi-element spidergrams of the majority of the mafic and intermediate dykes display a clear subduction signature, except a subset, which cut the Palaeozoic of İstanbul and the upper part of the Upper Cretaceous volcanics in the north of İstanbul (i.e. feeder dykes of the Kısırkaya Formation) and show a clear ocean island basalt (OIB) signature indicating that the melts feeding the dyke system during the Upper Cretaceous–Paleocene period were derived from two contrasting mantle sources: (1) initially a lithospheric mantle modified by subducted slab-derived melts which sourced the magmas with a clear subduction signature; and (2) followed by an asthenospheric mantle from which basic magmas with OIB signature. Petrological models indicate the interaction of these two discrete magma series via magma-mixing processes.

Geothermometric calculations based on the composition of amphiboles are in the range of 769–953 and 938–994°C. Geobarometric calculations indicate crystallization depths ranging over an interval between 3.0 and 20.2 km, implying a polybaric crystallization. The oxygen fugacity (logƒO
2
) values vary between −10.10 and −13.07 bar in the dykes cutting the Upper Cretaceous volcanics, and from −8.71 to −10.33 bar in intermediate dykes cutting the İstanbul Palaeozoic unit. H
2
O
melt
contents change between 4.91–6.89 and 4.82–7.51%, respectively implying that the dykes were emplaced at mid to shallow crustal levels. Dyke complexes of the İstanbul zone are interpreted to have been emplaced in a rifted volcanic arc margin related to the opening of the Black Sea during the Late Cretaceous–Paleocene period.
Statistical Optimization of FinFET Processor Architectures under PVT Variations Using Dual Device-Type Assignment
Authors: Yu Ye , Jha Niraj K.
Published: September 2017

With semiconductor technology scaling to the 22nm node and beyond, fin field-effect transistor (FinFET) has started replacing complementary metal-oxide semiconductor (CMOS), thanks to its superior control of short-channel effects and much lower leakage current. However, process, supply voltage, and temperature (PVT) variations across the integrated circuit (IC) become worse with technology scaling. Thus, to analyze timing, leakage power, and dynamic power under PVT variations, statistical analysis/optimization techniques are more suitable than traditional static timing/power analysis and optimization counterparts. In this article, we propose a statistical optimization framework using dual device-type assignment at the architecture level under PVT variations that takes spatial correlations into account and leverages circuit-level statistical analysis techniques. To the best of our knowledge, this is the first work to study statistical optimization at the system level under PVT variations. Simulation results show that leakage power yield and dynamic power yield at the mean value of the baseline can be improved by up to 44.2% and 21.2%, respectively, with no loss in timing yield for a single-core processor and up to 43.0% and 50.0%, respectively, without any loss in timing yield for an 8-core chip multiprocessor (CMP), at little area overhead. Under the same (99.0%) power yield constraints, leakage power and dynamic power are reduced by up to 91.2% and 4.3%, respectively, for a single-core processor, and up to 44.6% and 12.5%, respectively, for an 8-core CMP, with no loss in timing yield. We also show that optimizations performed without taking module-to-module and core-to-core spatial correlations into account overestimate yield, establishing the importance of taking such correlations into account.
Decrease in Anti-HBs Antibodies over Time in Medical Students and Healthcare Workers after Hepatitis B Vaccination
Authors: Sahana H. V. , Sarala N. , Prasad S. R.
Published: September 2017

Background. Hepatitis B is one of the most important occupational hazards among healthcare workers (HCWs). This study aimed to measure the anti-HBs titres among the medical students and HCWs vaccinated against hepatitis B virus and to determine the association between anti-HBs levels and time since vaccination. Materials and Methods. In this cross-sectional study, medical students and healthcare workers who had received all three doses of hepatitis B vaccination and completed at least six months after vaccination since the last dose were included. 3 ml blood was collected from subjects (n=340) and anti-HBs titre was estimated using ELISA. Results. A total of 340/400 subjects were aged between 18 and 60 years; 204 were females and 136 males. The median and interquartile range for time since vaccination were 5 and 5 years, respectively. Duration since vaccination was ≤5 years in 223 (65.5%), 6–10 years in 84 (24.7%), and >10 years in 33 (9.70%); among them, antibody titres were >10 mIU/ml in 94.1%, 79.7%, and 72.7% subjects, respectively. There was significant decline in antibody titres as duration of postvaccination increased. Conclusion. The proportion of subjects who were unprotected after 5 and 10 years after vaccination were 20% and 27%, respectively. The need for a booster dose can be made mandatory at least for healthcare professionals.
Effects of Brucine on the OPG/RANKL/RANK Signaling Pathway in MDA‐MB‐231 and MC3T3‐E1 Cell Coculture System
Authors: Wu Ruixian , Li Qian , Pei Xiaohua , Hu Kefei
Published: September 2017

The present study examined the effects of brucine on the OPG/RANKL/RANK signaling pathway for exploring the mechanism of brucine suppression of bone metastasis in breast cancer. MDA‐MB‐231 breast cancer cells and mouse osteoblast MC3T3‐E1 cells were cocultured to mimic the breast cancer bone metastasis microenvironment in vitro. qRT‐PCR and Western blotting were used to detect the expressions of OPG and RANKL at the mRNA and protein levels, respectively, in brucine‐treated cultures and they were compared to those in untreated cultures. We aimed to understand the effect of brucine on the entire OPG/RANKL/RANK signaling pathway after analyzing these effects. Results showed that brucine treatment significantly increased both the OPG mRNA/RANKL mRNA expression ratio and the OPG protein/RANKL protein ratio in cocultures compared to those in untreated cocultures (P < 0.01). Brucine, therefore, plays a regulatory role in the OPG/RANKL/RANK signaling pathway, suggesting that it can indirectly control osteoclasts by regulating the expression and secretion of OPG and RANKL in osteoblast cells, thereby inhibiting the differentiation and bone resorption function of osteoclasts.
Phenotypic Description of the Spanish Multicentre Genetic Glaucoma Group Cohort
Authors: Milla Elena , Gamundi Maria José , Duch Susana , Rios Jose , Carballo Miguel , Study Group EMEIGG
Published: September 2017

Introduction. The aim of the study was to make a phenotypic description of the Spanish multicentre glaucoma group cohort of patients. Design. Retrospective, observational, multicentre, cohort study. Material and Methods. The clinical charts of 152 patients with hereditary glaucoma from18 Spanish eye centres were reviewed in order to make an epidemiologic description of the type of glaucoma and associated factors. True hereditary cases were compared with familiar cases according to the Gong et al. criteria. Results. 61% were true hereditary cases and 39% familiar cases. Ocular comorbidity, optic disc damage, and visual field mean defect were significantly more severe in hereditary patients, who required significantly more first-line hypotensive drugs and surgical interventions to control intraocular pressure than familiar patients. Conclusions. The strength of the hereditary component of glaucoma seems to worsen the clinical course, causing more structural and functional damage and requiring more intense glaucoma treatment. The family history of glaucoma should be carefully investigated and taken into consideration when making treatment decisions or intensifying previous treatment.
Colorectal Cancer Blood-Based Biomarkers
Authors: Hauptman Nina , Glavač Damjan
Published: September 2017

Mortality and morbidity associated with colorectal cancer (CRC) are increasing globally, partly due to lack of early detection of the disease. The screening is usually performed with colonoscopy, which is invasive and unpleasant, discouraging participation in the screening. As a source of noninvasive and easily accessible biomarkers, liquid biopsies are emerging. Blood-based biomarkers have the potential as diagnostic and prognostic tool in CRC. Early stage detection of CRC with high sensitivity and specificity would likely lead to higher participation in the screening test. It would also improve the prognosis of the disease and improve the recurrence risk. In this review, we summarize the potential biomarkers for early detection and monitoring of CRC.
Prevalence of Chronic Pain, Treatments, Perception, and Interference on Life Activities: Brazilian Population-Based Survey
Authors: Souza Juliana Barcellos de , Grossmann Eduardo , Perissinotti Dirce Maria Navas , Oliveira Junior Jose Oswaldo de , Fonseca Paulo Renato Barreiros da , Posso Irimar de Paula
Published: September 2017

Background and Objectives. Chronic pain affects between 30% and 50% of the world population. Our objective was to estimate the prevalence of chronic pain in Brazil, describe and compare differences between pain types and characteristics, and identify the types of therapies adopted and the impact of pain on daily life. Methods. Cross-sectional study of a population-based survey with randomized sample from a private database. The interviews were conducted by phone. 78% of the respondents aged 18 years or more agreed to be interviewed, for a total of 723 respondents distributed throughout the country. Independent variables were demographic data, pain and treatment characteristics, and impact of pain on daily life. Comparative and associative statistical analyses were conducted to select variables for nonhierarchical logistic regression. Results. Chronic pain prevalence was 39% and mean age was 41 years with predominance of females (56%). We found higher prevalence of chronic pain in the Southern and Southeastern regions. Pain treatment was not specific to gender. Dissatisfaction with chronic pain management was reported by 49% of participants. Conclusion. 39% of interviewed participants reported chronic pain, with prevalence of females. Gender-associated differences were found in intensity perception and interference of pain on daily life activities.
Effective Models of Quantum Gravity Induced by Planck Scale Modifications in the Covariant Quantum Algebra
Authors: de Brito G. P. , Caneda P. I. C. , Gomes Y. M. P. , Guaitolini Junior J. T. , Nikoofard V.
Published: September 2017

We introduce modified covariant quantum algebra based on the so-called Quesne-Tkachuk algebra. By means of a deformation procedure we arrive at a class of higher-derivative models of gravity. The study of the particle spectra of these models reveals equivalence with the physical content of the well-known higher-derivative gravities. The particle spectrum exhibits the presence of spurious complex ghosts and, in light of this problem, we suggest an interesting interpretation in the context of minimal length theories. Also, a discussion regarding the nonrelativistic potential energy is proposed.
A Hierarchical Approach for Fast Calculating Minimal Cut Sets of a Microgrid
Authors: Che Yanbo , Zhao Yuancheng , Xu Jianmei , Zhou Jinhuan
Published: September 2017

Minimal cut sets are the basis of reliability analysis using analytical techniques. At the present stage, minimal cut sets are mainly obtained by dealing with minimal path sets, which involves cumbersome steps and slower operational speed. The speed of reliability analysis is limited by that of calculating minimal cut sets. In consideration of the characteristics of microgrid, a hierarchical approach for fast calculating minimal cut sets is proposed in this paper. Firstly, an equivalent principle is proposed to convert topology structure into network node diagram; then grades of nodes are designated based on their original connection and the breadth‐first search approach; afterwards, root-leaf matrices and selected matrix are created to specify the direction and order of the search. Next, all possible combinations of minimal cut sets are vertically traversed out by replacing root nodes with leaf nodes to achieve a more rapid access to minimal cut sets. Finally, taking the electrical structure of type A380 more electric aircraft as an example, mainstream methods are compared to show the correctness and advantage of our proposed method.
Polysaccharides fromTrichosanthes Fructusvia Ultrasound-Assisted Enzymatic Extraction Using Response Surface Methodology
Authors: Chen Fujia , Li Dahong , Shen Hongqi , Wang Chunhong , Li Enzhong , Xing Huihui , Guo Li , Zhao Qingchun , Shi Junhao , Nguyen Hoang , Liu Jiayang
Published: September 2017

An efficient procedure for ultrasound-assisted enzymatic extraction of crude polysaccharides fromTrichosanthes Fructus(crude TFP) using response surface methodology (RSM) was developed. The Box–Behnken design was applied to optimize the effects of pH (X1), enzyme amount (X2), extraction temperature (X3), and liquid-to-solid ratio (X4) on the extraction. The statistical analysis indicated that the independent variables (X4,X2, andX3), the quadratic coefficients (X12,X22,X32, andX42), and the interaction coefficient (X1X3) had significant impact on the yield of crude TFP. The optimal conditions were determined as follows: pH 4.5, enzyme amount 5000 u/g, extraction temperature 45°C, and liquid-to-solid ratio 30 ml/g. The experimental yield of crude TFP was 6.58%, which was very close to the predicted yield of 6.71%. TFPI was then purified and characterized with Sephadex G-100 column, UV-Vis, GPC, and FT-IR. The average molecular weight of TFPI was calculated to be 1.49 × 105 Da. TFPI exhibited strong reducing power and possessed not only remarkable scavenging activities against ABTS•+and DPPH radicals, but also high antitumor activities in C4-2, DU145, and PC3 cells. The results suggest thatTrichosanthes Fructusand TFPI could be a novel potent natural medicine with antioxidant and antitumor activities.
Quantitative Analysis of the Relationship between Three Psychological Parameters Based on Swallowtail Catastrophe Model
Authors: Meiza Asti , Darwis Sutawanir , Gunawan Agus Yodi , Fitriana Efi
Published: September 2017

A sudden jump in the value of the state variable in a certain dynamical system can be studied through a catastrophe model. This paper presents an application of catastrophe model to solve psychological problems. Since we will have three psychological aspects or parameters, intelligence (I), emotion (E), and adversity (A), a Swallowtail catastrophe model is considered to be an appropriate one. Our methodology consists of three steps: solving the Swallowtail potential function, finding the critical points up to and including threefold degenerates, and fitting the model into our measured data. Using a polynomial curve fitting derived from the potential function of Swallowtail catastrophe model, relations among three parameters combinations are analyzed. Results show that there are catastrophe phenomena for each relation, meaning that a small change in one psychological aspect may cause a dramatic change in another aspect.
Distant Supervision with Transductive Learning for Adverse Drug Reaction Identification from Electronic Medical Records
Authors: Taewijit Siriwon , Theeramunkong Thanaruk , Ikeda Mitsuru
Published: September 2017

Information extraction and knowledge discovery regarding adverse drug reaction (ADR) from large-scale clinical texts are very useful and needy processes. Two major difficulties of this task are the lack of domain experts for labeling examples and intractable processing of unstructured clinical texts. Even though most previous works have been conducted on these issues by applying semisupervised learning for the former and a word-based approach for the latter, they face with complexity in an acquisition of initial labeled data and ignorance of structured sequence of natural language. In this study, we propose automatic data labeling by distant supervision where knowledge bases are exploited to assign anentity-levelrelation label for each drug-event pair in texts, and then, we use patterns for characterizing ADR relation. The multiple-instance learning with expectation-maximization method is employed to estimate model parameters. The method applies transductive learning to iteratively reassign a probability of unknown drug-event pair at the training time. By investigating experiments with 50,998 discharge summaries, we evaluate our method by varying large number of parameters, that is, pattern types, pattern-weighting models, and initial and iterative weightings of relations for unlabeled data. Based on evaluations, our proposed method outperforms the word-based feature for NB-EM (iEM), MILR, and TSVM with F1 score of 11.3%, 9.3%, and 6.5% improvement, respectively.