bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimation of Constraint Factor on the Relationship Between J Integral and CTOD for Offshore Structural Steel Weldments
Authors: Moon Dong-Hyun , Kim Deok-Geun , Lee Jeong-Soo , Lee Jae-Myung , Kim Myung-Hyun
Published: September 2015

Offshore structures are exposed to severe operating conditions because energy resource development has recently extended toward deeper seabed and lower temperature regions. Hence, fracture toughness evaluation for very thick and high strength steels is one of the most important parameters required for the structural integrity assessment of offshore structures. Fracture toughness is known as a property which describes the ability of a material containing a crack to resist unstable brittle fracture. Crack tip opening displacement (CTOD) and J integral are the most commonly employed parameters as fracture criteria in elastic plastic fracture mechanics (EPFM). There have been extensive research efforts to clarify the relationship between CTOD and J integral in elastic plastic regime. Plastic constraint factor (PCF) in the relationship between CTOD and J integral can serve as a parameter to characterize constraint effects in fracture involving plastic deformation. In this regard, the characteristics of the PCF are of significant importance in EPFM analysis. In this study, we evaluated fracture toughness of American Petroleum Institute (API) 2 W Gr. 50 steel in terms of CTOD in various temperatures using single edge notched bend (SENB) specimens. Test specimens are fabricated by submerged arc welding (SAW) and flux cored arc welding (FCAW). In addition, CTOD values are compared to absorbed impact energy with respect to the weld metal (WM) and heat affected zone (HAZ). Then, we investigated PCFs with respect to several regions of the weldment at various temperatures. Experimental values of PCFs were calculated and then compared against the predicted values according to the American Society for Testing and Materials (ASTM) standard. CTOD values of WM by SAW is found to be about three times higher than that of FCAW at −10 °C, and CTOD values calculated by the ASTM standard are approximately 30% lower than the CTOD according to British Standard (BS). In addition, the maximum of 40% discrepancy is observed in PCFs obtained between the experiment and the predicted values according to the ASTM standard. This may lead to too conservative fracture toughness estimation for the welded joints of API 2 W Gr. 50 steel when using PCF by ASTM. Based on the accurate estimated PCF values obtained from this study, it is believed that rational fracture design of offshore structures is possible.
Estimation of Cutter Deflection Based on Study of Cutting Force and Static Flexibility
Authors: Duan Xianyin , Peng Fangyu , Yan Rong , Zhu Zerun , Huang Kai , Li Bin
Published: September 2015

In the tool orientation planning for five-axis sculptured surface machining, the geometrical constraints are usually considered. Actually, the effect of nongeometrical constraints on tool orientation planning is also important. This paper studied one nongeometrical constraint which was cutting force induced static deflection under different tool orientations, and proposed a cutter deflection model based on that. In the study of the cutting force, the undeformed chip thickness in filleted end milling was modeled by geometrical analysis and coordinate transformation of points at the cutting edge. In study of static flexibility of multi-axis machine, static flexibility of the entire machining system was taken into consideration. The multi-axis machining system was divided into the transmission axes-handle (AH) end and the cutting tool end. The equivalent shank method was developed to calculate the static flexibility of the AH end. In this method, static flexibility anisotropy of the AH end was considered, and the equivalent lengths of the AH end were obtained from calibration experiments. In cutter deflection modeling, force manipulability ellipsoid (FME) was applied to analyze the static flexibility of the AH end in arbitrary directions. Based on the synthetic static flexibility and average cutting force, cutter deflections were derived and estimated through developing program realization. The predicted results were compared with the experimental data obtained by machining 300 M steel curved surface workpiece, and a good agreement was shown, which indicated the effectiveness of the cutter deflection model. Additional experiments of machining flat workpiece were performed, and the relationship of cutter deflections and tool orientations were revealed directly. This work could be further employed to optimize tool orientations for suppressing the surface errors due to cutter deflections and achieving higher machining accuracy.
The shape of terrestrial abundance distributions
Authors: Alroy John
Published: September 2015

Findings of a new, low-dominance distribution of terrestrial abundance: the double geometric.
Direct observation of an attosecond electron wave packet in a nitrogen molecule
Authors: Okino Tomoya , Furukawa Yusuke , Nabekawa Yasuo , Miyabe Shungo , Amani Eilanlou A. , Takahashi Eiji J. , Yamanouchi Kaoru , Midorikawa Katsumi
Published: September 2015

Attosecond electron wave packet in a molecule is captured by the pump-probe method with a-few-pulse attosecond pulse train.
Detection of argon in the coma of comet 67P/Churyumov-Gerasimenko
Authors: Balsiger Hans , Altwegg Kathrin , Bar-Nun Akiva , Berthelier Jean-Jacques , Bieler Andre , Bochsler Peter , Briois Christelle , Calmonte Ursina , Combi Michael , De Keyser Johan , Eberhardt Peter , Fiethe Björn , Fuselier Stephen A. , Gasc Sébastien , Gombosi Tamas I. , Hansen Kenneth C. , Hässig Myrtha , Jäckel Annette , Kopp Ernest , Korth Axel , Le Roy Lena , Mall Urs , Marty Bernard , Mousis Olivier , Owen Tobias , Rème Henri , Rubin Martin , Sémon Thierry , Tzou Chia-Yu , Waite J. Hunter , Wurz Peter
Published: September 2015

ROSINA/DFMS shows that comets of type 67P/CG likely did not significantly contribute to Earth’s volatile budget.
The chlorine isotope fingerprint of the lunar magma ocean
Authors: Boyce Jeremy W. , Treiman Allan H. , Guan Yunbin , Ma Chi , Eiler John M. , Gross Juliane , Greenwood James P. , Stolper Edward M.
Published: September 2015

The unusually heavy Cl of the Moon is related not to degassing of dry magmas but rather to the loss of Cl from the lunar magma ocean.
Hierarchical spin-orbital polarization of a giant Rashba system
Authors: Bawden Lewis , Riley Jonathan M. , Kim Choong H. , Sankar Raman , Monkman Eric J. , Shai Daniel E. , Wei Haofei I. , Lochocki Edward B. , Wells Justin W. , Meevasana Worawat , Kim Timur K. , Hoesch Moritz , Ohtsubo Yoshiyuki , Le Fèvre Patrick , Fennie Craig J. , Shen Kyle M. , Chou Fangcheng , King Phil D. C.
Published: September 2015

Angle-resolved photoemission reveals the emergence of complex orbital texture concomitant with spin splitting in the Rashba compound BiTeI.
Future extreme sea level seesaws in the tropical Pacific
Authors: Widlansky Matthew J. , Timmermann Axel , Cai Wenju
Published: September 2015

Using climate models forced by increasing greenhouse gases, we find a doubling in extreme sea levels in the tropical Pacific.
Molybdenum-Containing Nicotine Hydroxylase Genes in a Nicotine Degradation Pathway That Is a Variant of the Pyridine and Pyrrolidine Pathways
Authors: Yu Hao , Tang Hongzhi , Li Yangyang , Xu Ping
Published: September 2015

Ochrobactrum
sp. strain SJY1 utilizes nicotine as a sole source of carbon, nitrogen, and energy via a variant of the pyridine and pyrrolidine pathways (the VPP pathway). Several strains and genes involved in the VPP pathway have recently been reported; however, the first catalyzing step for enzymatic turnover of nicotine is still unclear. In this study, a nicotine hydroxylase for the initial hydroxylation step of nicotine degradation was identified and characterized. The nicotine hydroxylase (VppA), which converts nicotine to 6-hydroxynicotine in the strain SJY1, is encoded by two open reading frames (
vppA
S
and
vppA
L
[subunits S and L, respectively]). The
vppA
genes were heterologously expressed in the non-nicotine-degrading strains
Escherichia coli
DH5α and
Pseudomonas putida
KT2440; only the
Pseudomonas
strain acquired the ability to degrade nicotine. The small subunit of VppA contained a [2Fe-2S] cluster-binding domain, and the large subunit of VppA contained a molybdenum cofactor-binding domain; however, an FAD-binding domain was not found in VppA. Resting cells cultivated in a molybdenum-deficient medium had low nicotine transformation activity, and excess molybdenum was detected in the purified VppA by inductively coupled plasma-mass spectrometry analysis. Thus, it is demonstrated that VppA is a two-component molybdenum-containing hydroxylase.
Sample Dilution and Bacterial Community Composition Influence Empirical Leucine-to-Carbon Conversion Factors in Surface Waters of the World's Oceans
Authors: Teira Eva , Hernando-Morales Víctor , Cornejo-Castillo Francisco M. , Alonso-Sáez Laura , Sarmento Hugo , Valencia-Vila Joaquín , Serrano Catalá Teresa , Hernández-Ruiz Marta , Varela Marta M. , Ferrera Isabel , Gutiérrez Morán Xosé Anxelu , Gasol Josep M.
Published: September 2015

The transformation of leucine incorporation rates to prokaryotic carbon production rates requires the use of either theoretical or empirically determined conversion factors. Empirical leucine-to-carbon conversion factors (eCFs) vary widely across environments, and little is known about their potential controlling factors. We conducted 10 surface seawater manipulation experiments across the world's oceans, where the growth of the natural prokaryotic assemblages was promoted by filtration (i.e., removal of grazers [F treatment]) or filtration combined with dilution (i.e., also relieving resource competition [FD treatment]). The impact of sunlight exposure was also evaluated in the FD treatments, and we did not find a significant effect on the eCFs. The eCFs varied from 0.09 to 1.47 kg C mol Leu
−1
and were significantly lower in the FD than in the F samples. Also, changes in bacterial community composition during the incubations, as assessed by automated ribosomal intergenic spacer analysis (ARISA), were more pronounced in the FD than in the F treatments, compared to unmanipulated controls. Thus, we discourage the common procedure of diluting samples (in addition to filtration) for eCF determination. The eCFs in the filtered treatment were negatively correlated with the initial chlorophyll
a
concentration, picocyanobacterial abundance (mostly
Prochlorococcus
), and the percentage of heterotrophic prokaryotes with high nucleic acid content (%HNA). The latter two variables explained 80% of the eCF variability in the F treatment, supporting the view that both
Prochlorococcus
and HNA prokaryotes incorporate leucine in substantial amounts, although this results in relatively low carbon production rates in the oligotrophic ocean.
Prevalence and Distribution of Listeria monocytogenes
inlA
Alleles Prone to Phase Variation and
inlA
Alleles with Premature Stop Codon Mutations among Human, Food, Animal, and Environmental Isolates
Authors: Manuel Clyde S. , Van Stelten Anna , Wiedmann Martin , Nightingale Kendra K. , Orsi Renato H.
Published: September 2015

In
Listeria monocytogenes
, 18 mutations leading to premature stop codons (PMSCs) in the virulence gene
inlA
have been identified to date. While most of these mutations represent nucleotide substitutions, a frameshift deletion in a 5′ seven-adenine homopolymeric tract (HT) in
inlA
has also been reported. This HT may play a role in phase variation and was first identified among
L. monocytogenes
lineage II ribotype DUP-1039C isolates. In order to better understand the distribution of different
inlA
mutations in this ribotype, a newly developed multiplex real-time PCR assay was used to screen 368 DUP-1039C isolates from human, animal, and food-associated sources for three known 5′
inlA
HT alleles: (i) wild-type (WT) (A
7
), (ii) frameshift (FS) (A
6
), and (iii) guanine interruption (A
2
GA
4
) alleles. Additionally, 228 DUP-1039C isolates were screened for all
inlA
PMSCs; data on the presence of all
inlA
PMSCs for the other 140 isolates were obtained from previous studies. The statistical analysis based on 191 epidemiologically unrelated strains showed that strains with
inlA
PMSC mutations (
n
= 41) were overrepresented among food-associated isolates, while strains encoding full-length InlA (
n
= 150) were overrepresented among isolates from farm animals and their environments. Furthermore, the A
6
allele was overrepresented and the A
7
allele was underrepresented among food isolates, while the A
6
allele was underrepresented among farm and animal isolates. Our results indicate that genetic variation in
inlA
contributes to niche adaptation within the lineage II subtype DUP-1039C.
Metabolic Adaptations of Azospirillum brasilense to Oxygen Stress by Cell-to-Cell Clumping and Flocculation
Authors: Bible Amber N. , Khalsa-Moyers Gurusahai K. , Mukherjee Tanmoy , Green Calvin S. , Mishra Priyanka , Purcell Alicia , Aksenova Anastasia , Hurst Gregory B. , Alexandre Gladys
Published: September 2015

The ability of bacteria to monitor their metabolism and adjust their behavior accordingly is critical to maintain competitiveness in the environment. The motile microaerophilic bacteriumAzospirillum brasilensenavigates oxygen gradients by aerotaxis in order to locate low oxygen concentrations that can support metabolism. When cells are exposed to elevated levels of oxygen in their surroundings, motileA. brasilensecells implement an alternative response to aerotaxis and form transient clumps by cell-to-cell interactions. Clumping was suggested to represent a behavior protecting motile cells from transiently elevated levels of aeration. Using the proteomics of wild-type and mutant strains affected in the extent of their clumping abilities, we show that cell-to-cell clumping represents a metabolic scavenging strategy that likely prepares the cells for further metabolic stresses. Analysis of mutants affected in carbon or nitrogen metabolism confirmed this assumption. The metabolic changes experienced as clumping progresses prime cells for flocculation, a morphological and metabolic shift of cells triggered under elevated-aeration conditions and nitrogen limitation. The analysis of various mutants during clumping and flocculation characterized an ordered set of changes in cell envelope properties accompanying the metabolic changes. These data also identify clumping and early flocculation to be behaviors compatible with the expression of nitrogen fixation genes, despite the elevated-aeration conditions. Cell-to-cell clumping may thus license diazotrophy to microaerophilicA. brasilensecells under elevated oxygen conditions and prime them for long-term survival via flocculation if metabolic stress persists.
Contrast encephalopathy after coiling in the setting of obstructive sleep apnoea
Authors: Liu Jonathan J , Dahlin Brian C , Waldau Ben
Published: September 2015

Obstructive sleep apnoea (OSA) is increasingly recognised as a source of perioperative morbidity and mortality. We describe a patient with severe OSA who developed transient contrast encephalopathy after elective coiling of an anterior communicating artery aneurysm. Contrast extravasation led to cerebral oedema, seizures and delirium, which eventually completely resolved. OSA is known to be associated with a proinflammatory state that leads to hypertension, impaired endothelial repair capacity and endothelial dysfunction. Further studies are needed to clarify whether OSA increases the risk of endovascular procedures.
The effect of statins on average survival in randomised trials, an analysis of end point postponement
Authors: Kristensen Malene Lopez , Christensen Palle Mark , Hallas Jesper
Published: September 2015

Objective

To estimate the average postponement of death in statin trials.

Setting

A systematic literature review of all statin trials that presented all-cause survival curves for treated and untreated.

Intervention

Statin treatment compared to placebo.

Primary outcome measures

The average postponement of death as represented by the area between the survival curves.

Results

6 studies for primary prevention and 5 for secondary prevention with a follow-up between 2.0 and 6.1 years were identified. Death was postponed between −5 and 19 days in primary prevention trials and between −10 and 27 days in secondary prevention trials. The median postponement of death for primary and secondary prevention trials were 3.2 and 4.1 days, respectively.

Conclusions

Statin treatment results in a surprisingly small average gain in overall survival within the trials’ running time. For patients whose life expectancy is limited or who have adverse effects of treatment, withholding statin therapy should be considered.
Determinants of caregivers’ vaccination intention with respect to child age group: a cross-sectional survey in South Korea
Authors: Paek Hye-Jin , Shin Kyung-Ah , Park Kisoo
Published: September 2015

Objective

This study examined how knowledge, risk perception, health beliefs and multidimensional health locus of control (HLC) were associated with caregivers’ intention to vaccinate their child, and how these associations varied across child age groups.

Setting

South Korea.

Methods

The cross-sectional survey was conducted via a face-to-face interview among 1017 nationally representative caregivers who had children aged 12 or younger. The outcome variable was caregivers’ intention to vaccinate their children.

Results

Hierarchical regression analysis indicated that risk perception was negatively associated with vaccination intention only among the age group 4–6 (β=−0.127, p<0.05). Perceived benefit was the only significant predictor of the outcome variables for all three age groups. In contrast, perceived barrier was negatively related to vaccination intention only among the age group 7–12 (β=−0.104, p<0.05). Internal HLC was positively related to vaccination intention only among the age group 7–12 (β=0.151, p<0.001), while chance HLC was negatively related to vaccination intention only among the age group 0–3 (β=−0.121, p<0.05).

Conclusions

This study identifies key vaccination intention determinants that are differentially associated with caregivers’ children's age groups. To improve vaccination rates, it suggests the need for strategies tailored to children's age.
Prevalence of multimorbidity in the adult population attending primary care in Portugal: a cross-sectional study
Authors: Prazeres Filipe , Santiago Luiz
Published: September 2015

Objectives

To determine the prevalence of multimorbidity in the adult population attending primary care in Portugal, to identify associated sociodemographic factors, and to reveal combinations of chronic health problems.

Design

Cross-sectional, analytical study.

Setting

Primary Care Centres in mainland Portugal across the five Portuguese Healthcare Administrative Regions.

Participants

1279 women and 714 men agreed to participate. The mean age was 56.3 years (59.0 years for men; 54.8 years for women). The most frequent marital status was married/cohabiting (69.5%). The most predominant living arrangement was living as a couple (57.2%). A considerable proportion consisted of pensioners/retirees (41.5%) and adults with a low educational level (48.7%). Sufficient monthly income was reported in 54.4% of the cases.

Primary outcome measures

For each patient, multimorbidity was measured either by the presence of ≥2 or ≥3 chronic health problems, from a list of 147 chronic health problems. Clinical data were collected using the general practitioner's knowledge of the patient's history, patient's self-report and medical records. Cluster analyses were performed to reveal distinct patterns of multimorbidity.

Secondary outcome measures

Patient social and demographic data (sex, age, residence area, current marital status, number of years of formal education, living arrangements, professional status and self-perceived economic status). Logistic regression analyses were performed to determine the association between sociodemographic factors and multimorbidity.

Results

Multimorbidity (2 or more chronic health problems) was present in 72.7%. When a cut-off of three or more was used, an expressive percentage of multimorbidity (57.2%) remained present. The likelihood of having multimorbidity increased significantly with age. Pensioners/retirees and adults with low levels of education were significantly more likely to suffer from multimorbidity. Cardiometabolic and mental disorders were the most common chronic health problems. Six multimorbidity clusters have been identified.

Conclusions

Multimorbidity was found to be a common occurrence in the Portuguese primary care users. Future primary healthcare policies should take multimorbidity into consideration.
One size fits all? Mixed methods evaluation of the impact of 100% single-room accommodation on staff and patient experience, safety and costs
Authors: Maben Jill , Griffiths Peter , Penfold Clarissa , Simon Michael , Anderson Janet E , Robert Glenn , Pizzo Elena , Hughes Jane , Murrells Trevor , Barlow James
Published: September 2015

Background and objectives

There is little strong evidence relating to the impact of single-room accommodation on healthcare quality and safety. We explore the impact of all single rooms on staff and patient experience; safety outcomes; and costs.

Methods

Mixed methods pre/post ‘move’ comparison within four nested case study wards in a single acute hospital with 100% single rooms; quasi-experimental before-and-after study with two control hospitals; analysis of capital and operational costs associated with single rooms.

Results

Two-thirds of patients expressed a preference for single rooms with comfort and control outweighing any disadvantages (sense of isolation) felt by some. Patients appreciated privacy, confidentiality and flexibility for visitors afforded by single rooms. Staff perceived improvements (patient comfort and confidentiality), but single rooms were worse for visibility, surveillance, teamwork, monitoring and keeping patients safe. Staff walking distances increased significantly post move. A temporary increase of falls and medication errors in one ward was likely to be associated with the need to adjust work patterns rather than associated with single rooms per se. We found no evidence that single rooms reduced infection rates. Building an all single-room hospital can cost 5% more with higher housekeeping and cleaning costs but the difference is marginal over time.

Conclusions

Staff needed to adapt their working practices significantly and felt unprepared for new ways of working with potentially significant implications for the nature of teamwork in the longer term. Staff preference remained for a mix of single rooms and bays. Patients preferred single rooms.
Differential expression of ribosomal proteins in myelodysplastic syndromes
Authors: Rinker Elizabeth B , Dueber Julie C , Qualtieri Julianne , Tedesco Jason , Erdogan Begum , Bosompem Amma , Kim Annette S
Published: September 2015

Aberrations of ribosomal biogenesis have been implicated in several congenital bone marrow failure syndromes, such as Diamond–Blackfan anaemia, Shwachman–Diamond syndrome and Dyskeratosis Congenita. Recent studies have identified haploinsufficiency ofRPS14in the acquired bone marrow disease isolated 5q minus syndrome, a subtype of myelodysplastic syndromes (MDS). However, the expression of various proteins comprising the ribosomal subunits and other proteins enzymatically involved in the synthesis of the ribosome has not been explored in non-5q minus MDS. Furthermore, differences in the effects of these expression alterations among myeloid, erythroid and megakaryocyte lineages have not been well elucidated. We examined the expression of several proteins related to ribosomal biogenesis in bone marrow biopsy specimens from patients with MDS (5q minus patients excluded) and controls with no known myeloid disease. Specifically, we found that there is overexpression of RPS24, DKC1 and SBDS in MDS. This overexpression is in contrast to the haploinsufficiency identified in the congenital bone marrow failure syndromes and in acquired 5q minus MDS. Potential mechanisms for these differences and aetiology for these findings in MDS are discussed.
Estimated levels of safety for small unmanned aerial vehicles and risk mitigation strategies
Authors: Stevenson Jonathan D. , O’Young Siu , Rolland Luc
Published: September 2015

In this paper the risks posed by small unmanned aerial vehicles (UAV) 1 are determined using quantitative methods, to calculate the estimated level of safety (ELS). The aim is to determine if the use of small UAVs for typical low altitude long endurance missions creates any increased risk versus manned aviation accident rates. The risk discussion includes both perceived concerns with the small UAV and the real physical risks posed. Once the ELS is known, possible mitigation methods are presented that may improve the safety of the small UAV to a level where it may considered as having an equivalent level of safety as manned aircraft operating in the same unsegregated civilian airspace.
Measurement of distributions of cesium and rubidium in rice grains using micro-PIXE for detailed examinations of contaminated food
Authors: Koshio S. , Ishii K. , Matsuyama S. , Terakawa A. , Fujiwara M. , Watanabe K. , Oshikawa S. , Kikuchi K. , Itoh S. , Kasahara K. , Toyama S. , Suzuki Y. , Matsuyama T. , Kamiya T. , Satoh T. , Koka M. , Kitamura A.
Published: September 2015

We used micro-PIXE to investigate the distribution of Cs and Rb in rice grains. We succeeded, for the first time, in measuring the elemental distributions in entire rice grains (with dimensions of 6.25 mm [Formula: see text] 6.25 mm) at micrometer spatial resolution. We found that Cs and Rb accumulated in the bran and germ of the rice. The distributions of P, K, Rb and Cs were similar within the rice grain. The concentrations of Cs and Rb in the rice were proportional to those in the soil, as well as to the exposure time. The uptake of Rb was significantly larger than that of Cs. Furthermore, the behavior of Rb was similar to that of Cs in the micrometer-scale regions in plants. It follows that the distribution of Rb can be used to investigate the behavior of radioactive Cs in plants.
Low-dose radiation affects cardiac physiology: gene networks and molecular signaling in cardiomyocytes
Authors: Coleman Matthew A. , Sasi Sharath P. , Onufrak Jillian , Natarajan Mohan , Manickam Krishnan , Schwab John , Muralidharan Sujatha , Peterson Leif E. , Alekseyev Yuriy O. , Yan Xinhua , Goukassian David A.
Published: September 2015

There are 160,000 cancer patients worldwide treated with particle radiotherapy (RT). With the advent of proton, and high (H) charge (Z) and energy (E) HZE ionizing particle RT, the cardiovascular diseases risk estimates are uncertain. In addition, future deep space exploratory-type missions will expose humans to unknown but low doses of particle irradiation (IR). We examined molecular responses using transcriptome profiling in left ventricular murine cardiomyocytes isolated from mice that were exposed to 90 cGy, 1 GeV proton (1H) and 15 cGy, 1 GeV/nucleon iron (56Fe) over 28 days after exposure. Unsupervised clustering analysis of gene expression segregated samples according to the IR response and time after exposure, with56Fe-IR showing the greatest level of gene modulation.1H-IR showed little differential transcript modulation. Network analysis categorized the major differentially expressed genes into cell cycle, oxidative responses, and transcriptional regulation functional groups. Transcriptional networks identified key nodes regulating expression. Validation of the signal transduction network by protein analysis and gel shift assay showed that particle IR clearly regulates a long-lived signaling mechanism for ERK1/2, p38 MAPK signaling and identified NFATc4, GATA4, STAT3, and NF-κB as regulators of the response at specific time points. These data suggest that the molecular responses and gene expression to56Fe-IR in cardiomyocytes are unique and long-lasting. Our study may have significant implications for the efforts of National Aeronautics and Space Administration to develop heart disease risk estimates for astronauts and for patients receiving conventional and particle RT via identification of specific HZE-IR molecular markers.
Role of atrial tissue remodeling on rotor dynamics: an in vitro study
Authors: Climent Andreu M. , Guillem María S , Fuentes Lucia , Lee Peter , Bollensdorff Christian , Fernández-Santos María Eugenia , Suárez-Sancho Susana , Sanz-Ruiz Ricardo , Sánchez Pedro Luis , Atienza Felipe , Fernández-Avilés Francisco
Published: September 2015

The objective of this article is to present an in vitro model of atrial cardiac tissue that could serve to study the mechanisms of remodeling related to atrial fibrillation (AF). We analyze the modification on gene expression and modifications on rotor dynamics following tissue remodeling. Atrial murine cells (HL-1 myocytes) were maintained in culture after the spontaneous initiation of AF and analyzed at two time points: 3.1 ± 1.3 and 9.7 ± 0.5 days after AF initiation. The degree of electrophysiological remodeling (i.e., relative gene expression of key ion channels) and structural inhomogeneity was compared between early and late cell culture times both in nonfibrillating and fibrillating cell cultures. In addition, the electrophysiological characteristics of in vitro fibrillation [e.g., density of phase singularities (PS/cm2), dominant frequency, and rotor meandering] analyzed by means of optical mapping were compared with the degree of electrophysiological remodeling. Fibrillating cell cultures showed a differential ion channel gene expression associated with atrial tissue remodeling (i.e., decreased SCN5A, CACN1C, KCND3, and GJA1 and increased KCNJ2) not present in nonfibrillating cell cultures. Also, fibrillatory complexity was increased in late- vs. early stage cultures (1.12 ± 0.14 vs. 0.43 ± 0.19 PS/cm2, P < 0.01), which was associated with changes in the electrical reentrant patterns (i.e., decrease in rotor tip meandering and increase in wavefront curvature). HL-1 cells can reproduce AF features such as electrophysiological remodeling and an increased complexity of the electrophysiological behavior associated with the fibrillation time that resembles those occurring in patients with chronic AF.
Leptin decreases heart rate associated with increased ventricular repolarization via its receptor
Authors: Lin Yen-Chang , Huang Jianying , Hileman Stan , Martin Karen H. , Hull Robert , Davis Mary , Yu Han-Gang
Published: September 2015

Leptin has been proposed to modulate cardiac electrical properties via β-adrenergic receptor activation. The presence of leptin receptors and adipocytes in myocardium raised a question as to whether leptin can directly modulate cardiac electrical properties such as heart rate and QT interval via its receptor. In this work, the role of local direct actions of leptin on heart rate and ventricular repolarization was investigated. We identified the protein expression of leptin receptors at cell surface of sinus node, atrial, and ventricular myocytes isolated from rat heart. Leptin at low doses (0.1–30 μg/kg) decreased resting heart rate; at high doses (150–300 μg/kg), leptin induced a biphasic effect (decrease and then increase) on heart rate. In the presence of high-dose propranolol (30 mg/kg), high-dose leptin only reduced heart rate and sometimes caused sinus pauses and ventricular tachycardia. The leptin-induced inhibition of resting heart rate was fully reversed by leptin antagonist. Leptin also increased heart rate-corrected QT interval (QTc), and leptin antagonist did not. In isolated ventricular myocytes, leptin (0.03–0.3 μg/ml) reversibly increased the action potential duration. These results supported our hypothesis that in addition to indirect pathway via sympathetic tone, leptin can directly decrease heart rate and increase QT interval via its receptor independent of β-adrenergic receptor stimulation. During inhibition of β-adrenergic receptor activity, high concentration of leptin in myocardium can cause deep bradycardia, prolonged QT interval, and ventricular arrhythmias.
Revascularization of decellularized lung scaffolds: principles and progress
Authors: Stabler Collin T. , Lecht Shimon , Mondrinos Mark J. , Goulart Ernesto , Lazarovici Philip , Lelkes Peter I.
Published: September 2015

There is a clear unmet clinical need for novel biotechnology-based therapeutic approaches to lung repair and/or replacement, such as tissue engineering of whole bioengineered lungs. Recent studies have demonstrated the feasibility of decellularizing the whole organ by removal of all its cellular components, thus leaving behind the extracellular matrix as a complex three-dimensional (3D) biomimetic scaffold. Implantation of decellularized lung scaffolds (DLS), which were recellularized with patient-specific lung (progenitor) cells, is deemed the ultimate alternative to lung transplantation. Preclinical studies demonstrated that, upon implantation in rodent models, bioengineered lungs that were recellularized with airway and vascular cells were capable of gas exchange for up to 14 days. However, the long-term applicability of this concept is thwarted in part by the failure of current approaches to reconstruct a physiologically functional, quiescent endothelium lining the entire vascular tree of reseeded lung scaffolds, as inferred from the occurrence of hemorrhage into the airway compartment and thrombosis in the vasculature in vivo. In this review, we explore the idea that successful whole lung bioengineering will critically depend on 1) preserving and/or reestablishing the integrity of the subendothelial basement membrane, especially of the ultrathin respiratory membrane separating airways and capillaries, during and following decellularization and 2) restoring vascular physiological functionality including the barrier function and quiescence of the endothelial lining following reseeding of the vascular compartment. We posit that physiological reconstitution of the pulmonary vascular tree in its entirety will significantly promote the clinical translation of the next generation of bioengineered whole lungs.
Lung volume recruitment in a preterm pig model of lung immaturity
Authors: Arrindell Esmond L. , Krishnan Ramesh , van der Merwe Marie , Caminita Frank , Howard Scott C. , Zhang Jie , Buddington Randal K.
Published: September 2015

A translational preterm pig model analogous to infants born at 28 wk of gestation revealed that continuous positive airway pressure results in limited lung recruitment but does not prevent respiratory distress syndrome, whereas assist-control + volume guarantee (AC+VG) ventilation improves recruitment but can cause injury, highlighting the need for improved ventilation strategies. We determined whether airway pressure release ventilation (APRV) can be used to recruit the immature lungs of preterm pigs without injury. Spontaneously breathing pigs delivered at 89% of term (model for 28-wk infants) were randomized to 24 h of APRV ( n = 9) vs. AC+VG with a tidal volume of 5 ml/kg ( n = 10). Control pigs ( n = 36) were provided with supplemental oxygen by an open mask. Nutrition and fluid support was provided throughout the 24-h period. All pigs supported with APRV and AC+VG survived 24 h, compared with 62% of control pigs. APRV resulted in improved lung volume recruitment compared with AC+VG based on radiographs, lower Pco2levels (44 ± 2.9 vs. 53 ± 2.7 mmHg, P = 0.009) and lower inspired oxygen fraction requirements (36 ± 6 vs. 44 ± 11%, P < 0.001), and higher oxygenation index (5.1 ± 1.5 vs. 2.9 ± 1.1, P = 0.001). There were no differences between APRV and AC+VG pigs for heart rate, ratio of wet to dry lung mass, proinflammatory cytokines, or histopathological markers of lung injury. Lung protective ventilation with APRV improved recruitment of alveoli of preterm lungs, enhanced development and maintenance of functional residual capacity without injury, and improved clinical outcomes relative to AC+VG. Long-term consequences of lung volume recruitment by using APRV should be evaluated.
Multilayered Scattering Problem with Generalized Impedance Boundary Condition on the Core
Authors: Guo Jun , Yan Guozheng , Cai Mingjian
Published: September 2015

This paper is concerned with the scattering problem of time-harmonic acoustic plane waves by an impenetrable obstacle buried in a piecewise homogeneous medium. The so-called generalized impedance boundary condition is imposed on the boundary of the obstacle. Firstly, the well posedness of the solution to the direct scattering problem is established by using the boundary integral method. Then a uniqueness result for the inverse scattering problem is proved; that is, both of the obstacle’s shape and the impedances (μ,λ) can be uniquely determined from far field measurements. Furthermore, a mathematical basis is given to reconstruct the shape of the obstacle by using a modified linear sampling method.
Ecological Determinants of Forest to the Abundance ofLutzomyia longiflocosain Tello, Colombia
Authors: Rodríguez Serrezuela Ruthber , Carvajal Pinilla Luis Alexander
Published: September 2015

Lutzomyia longiflocosais considered the most likely vector of cutaneous leishmaniasis in the sub-Andean region of the upper valley of the Magdalena River between 1,000 and 2,000 meters in the Department of Huila, Colombia.L. longiflocosais anthropophilic, has endophagic behavior, and is especially important since its dominance in epidemics recorded in the last decade in the departments of Huila, Tolima, and the outbreak in Norte de Santander. The aim of our work is to identify ecological determinants in forest microhabitat level defining the abundance ofL. longiflocosa. We use sampling; this was performed in 56 microhabitats of 28 forests with CDC traps for two consecutive nights from 18:00 to 06:00 hours. Each microhabitat (favorable and unfavorable) was located 10 m from the ecotone, with an approximate area of 10 m2. Thirty-five variables were examined as potential explanatory variables which were recorded in each microhabitat. Regression models were used to identify ecological determinants. Our results confirm that there are favorable microhabitats in the forest with specific ecological determinants that define the aggregated distribution of the species and provide the conditions necessary for survival and abundance ofL. longiflocosa.
Subtoxic Concentrations of Hepatotoxic Drugs Lead to Kupffer Cell Activation in a Human In Vitro Liver Model: An Approach to Study DILI
Authors: Kegel Victoria , Pfeiffer Elisa , Burkhardt Britta , Liu Jia L. , Zeilinger Katrin , Nüssler Andreas K. , Seehofer Daniel , Damm Georg
Published: September 2015

Drug induced liver injury (DILI) is an idiosyncratic adverse drug reaction leading to severe liver damage. Kupffer cells (KC) sense hepatic tissue stress/damage and therefore could be a tool for the estimation of consequent effects associated with DILI. Aim of the present study was to establish a human in vitro liver model for the investigation of immune‐mediated signaling in the pathogenesis of DILI. Hepatocytes and KC were isolated from human liver specimens. The isolated KC yield was 1.2 ± 0.9 × 106 cells/g liver tissue with a purity of >80%. KC activation was investigated by the measurement of reactive oxygen intermediates (ROI, DCF assay) and cell activity (XTT assay). The initial KC activation levels showed broad donor variability. Additional activation of KC using supernatants of hepatocytes treated with hepatotoxic drugs increased KC activity and led to donor‐dependent changes in the formation of ROI compared to KC incubated with supernatants from untreated hepatocytes. Additionally, a compound‐ and donor‐dependent increase in proinflammatory cytokines or in anti‐inflammatory cytokines was detected. In conclusion, KC related immune signaling in hepatotoxicity was successfully determined in a newly established in vitro liver model. KC were able to detect hepatocyte stress/damage and to transmit a donor‐ and compound‐dependent immune response via cytokine production.
Text Matching and Categorization: Mining Implicit Semantic Knowledge from Tree-Shape Structures
Authors: Guo Lin , Zuo Wanli , Peng Tao , Yue Lin
Published: September 2015

The diversities of large-scale semistructured data make the extraction of implicit semantic information have enormous difficulties. This paper proposes an automatic and unsupervised method of text categorization, in which tree-shape structures are used to represent semantic knowledge and to explore implicit information by mining hidden structures without cumbersome lexical analysis. Mining implicit frequent structures in trees can discover both direct and indirect semantic relations, which largely enhances the accuracy of matching and classifying texts. The experimental results show that the proposed algorithm remarkably reduces the time and effort spent in training and classifying, which outperforms established competitors in correctness and effectiveness.
Unit-Specific Event-Based and Slot-Based Hybrid Model Framework with Hierarchical Structure for Short-Term Scheduling
Authors: Wang Yue , Su Hongye , Shao Hanshan , Xie Lei
Published: September 2015

Unit-specific event-based continuous-time model has inaccurate calculation problems in involving resource constraints, due to the heterogeneous locations of the event points for different units. In order to address this limitation, a continuous-time unit-specific event-based and slot-based hybrid model framework with hierarchical structure is proposed in this work. A unit-specific event-based model without utility constraints is formulated in upper layer, and a slot-based model is introduced in lower layer. In the hierarchical structure, the two layers jointly address the short-term production scheduling problem of batch plants under utility consideration. The key features of this work include the following: (a) eliminating overstrict constraints on utility resources, (b) solving multiple counting problems, and (c) considering duration time of event points in calculating utility utilization level. The effectiveness and advantages of proposed model are illustrated through two benchmark examples from the literatures.
Inactivation of the p53–KLF4–CEBPA Axis in Acute Myeloid Leukemia
Authors: Seipel Katja , Marques Miguel Teixera , Bozzini Marie-Ange , Meinken Christina , Mueller Beatrice U. , Pabst Thomas
Published: September 2015

Purpose: In acute myeloid leukemia (AML), the transcription factors CEBPA and KLF4 as well as the universal tumor suppressor p53 are frequently deregulated. Here, we investigated the extent of dysregulation, the molecular interactions, and the mechanisms involved.

Experimental Design: One hundred ten AML patient samples were analyzed for protein levels of CEBPA, KLF4, p53, and p53 modulators. Regulation of CEBPA gene expression by KLF4 and p53 or by chemical p53 activators was characterized in AML cell lines.

Results: We found that CEBPA gene transcription can be directly activated by p53 and KLF4, suggesting a p53–KLF4–CEBPA axis. In AML patient cells, we observed a prominent loss of p53 function and concomitant reduction of KLF4 and CEBPA protein levels. Assessment of cellular p53 modulator proteins indicated that p53 inactivation in leukemic cells correlated with elevated levels of the nuclear export protein XPO1/CRM1 and increase of the p53 inhibitors MDM2 and CUL9/PARC in the cytoplasm. Finally, restoring p53 function following treatment with cytotoxic chemotherapy compounds and p53 restoring non-genotoxic agents induced CEBPA gene expression, myeloid differentiation, and cell-cycle arrest in AML cells.

Conclusions: The p53–KLF4–CEBPA axis is deregulated in AML but can be functionally restored by conventional chemotherapy and novel p53 activating treatments. Clin Cancer Res; 22(3); 746–56. ©2015 AACR.
Unconjugated Bilirubin Is a Novel Prognostic Biomarker for Nasopharyngeal Carcinoma and Inhibits Its Metastasis via Antioxidation Activity
Authors: Deng Cheng-Cheng , Xu Miao , Li Jing , Luo Xiao-Lin , Zhu Yu-Jia , Jiang Rou , Zhang Meng-Xia , Lei Jin-Ju , Lian Yi-Fan , Zou Xiong , You Rui , Chen Li-Zhen , Feng Qi-Sheng , Bei Jin-Xin , Chen Ming-Yuan , Zeng Yi-Xin
Published: September 2015

Distant metastasis is the most common cause of treatment failure and mortality in nasopharyngeal carcinoma (NPC) patients. Thus, it is important to understand the mechanism of NPC metastasis and identify reliable prognostic factors. In this study, we investigated the prognostic value of unconjugated bilirubin (UCB), which was previously considered a byproduct of heme catabolism, in NPC patients and examined the effects of UCB on NPC metastasis. The receiver operating characteristic analysis–generated UCB cutoff point for DMFS was 9.7 μmol/L. We found that higher UCB levels were significantly associated with favorable distant metastasis-free survival (DMFS, 93.3% vs. 84.2%, P < 0.001) in NPC patients and was an independent predictor for DMFS (HR, 0.416; 95% confidence interval, 0.280–0.618; P < 0.001). We next found that UCB treatment impaired the invasion capability of NPC cells and potently inhibited lung metastasis of NPC cells in nude mice. Further investigation showed that UCB inhibited reactive oxygen species production, which is involved in the repression of ERK1/2 activation and matrix metalloproteinase-2 (MMP-2) expression. Moreover, lower levels of ERK1/2 phosphorylation and MMP-2 expression were observed in the NPC lung metastases of nude mice administered UCB. Taken together, our results indicate that UCB is a significantly favorable factor for DMFS in NPC patients and may play an important role in NPC chemoprevention. Cancer Prev Res; 9(2); 180–8. ©2015 AACR.
Infection Exposure Is a Causal Factor in B-cell Precursor Acute Lymphoblastic Leukemia as a Result ofPax5-Inherited Susceptibility
Authors: Martín-Lorenzo Alberto , Hauer Julia , Vicente-Dueñas Carolina , Auer Franziska , González-Herrero Inés , García-Ramírez Idoia , Ginzel Sebastian , Thiele Ralf , Constantinescu Stefan N. , Bartenhagen Christoph , Dugas Martin , Gombert Michael , Schäfer Daniel , Blanco Oscar , Mayado Andrea , Orfao Alberto , Alonso-López Diego , Rivas Javier De Las , Cobaleda César , García-Cenador Maria Begoña , García-Criado Francisco Javier , Sánchez-García Isidro , Borkhardt Arndt
Published: September 2015

Earlier in the past century, infections were regarded as the most likely cause of childhood B-cell precursor acute lymphoblastic leukemia (pB-ALL). However, there is a lack of relevant biologic evidence supporting this hypothesis. We present in vivo genetic evidence mechanistically connecting inherited susceptibility to pB-ALL and postnatal infections by showing that pB-ALL was initiated in Pax5 heterozygous mice only when they were exposed to common pathogens. Strikingly, these murine pB-ALLs closely resemble the human disease. Tumor exome sequencing revealed activating somatic, nonsynonymous mutations of Jak3 as a second hit. Transplantation experiments and deep sequencing suggest that inactivating mutations in Pax5 promote leukemogenesis by creating an aberrant progenitor compartment that is susceptible to malignant transformation through accumulation of secondary Jak3 mutations. Thus, treatment of Pax5+/− leukemic cells with specific JAK1/3 inhibitors resulted in increased apoptosis. These results uncover the causal role of infection in pB-ALL development.

Significance: These results demonstrate that delayed infection exposure is a causal factor in pB-ALL. Therefore, these findings have critical implications for the understanding of the pathogenesis of leukemia and for the development of novel therapies for this disease. Cancer Discov; 5(12); 1328–43. ©2015 AACR.

See related commentary by Greaves and Müschen, p. 1244.

This article is highlighted in the In This Issue feature, p. 1225