bluuebunny/crossref_metadata_2025 huggingface dataset:
High attenuation areas on chest computed tomography in community-dwelling adults: the MESA study
Authors: Podolanczuk Anna J. , Oelsner Elizabeth C. , Barr R. Graham , Hoffman Eric A. , Armstrong Hilary F. , Austin John H.M. , Basner Robert C. , Bartels Matthew N. , Christie Jason D. , Enright Paul L. , Gochuico Bernadette R. , Hinckley Stukovsky Karen , Kaufman Joel D. , Hrudaya Nath P. , Newell John D. , Palmer Scott M. , Rabinowitz Dan , Raghu Ganesh , Sell Jessica L. , Sieren Jered , Sonavane Sushil K. , Tracy Russell P. , Watts Jubal R. , Williams Kayleen , Kawut Steven M. , Lederer David J.
Published: July 2016

Evidence suggests that lung injury, inflammation and extracellular matrix remodelling precede lung fibrosis in interstitial lung disease (ILD). We examined whether a quantitative measure of increased lung attenuation on computed tomography (CT) detects lung injury, inflammation and extracellular matrix remodelling in community-dwelling adults sampled without regard to respiratory symptoms or smoking.

We measured high attenuation areas (HAA; percentage of lung voxels between −600 and −250 Hounsfield Units) on cardiac CT scans of adults enrolled in the Multi-Ethnic Study of Atherosclerosis.

HAA was associated with higher serum matrix metalloproteinase-7 (mean adjusted difference 6.3% per HAA doubling, 95% CI 1.3–11.5), higher interleukin-6 (mean adjusted difference 8.8%, 95% CI 4.8–13.0), lower forced vital capacity (FVC) (mean adjusted difference −82 mL, 95% CI −119–−44), lower 6-min walk distance (mean adjusted difference −40 m, 95% CI −1–−80), higher odds of interstitial lung abnormalities at 9.5 years (adjusted OR 1.95, 95% CI 1.43–2.65), and higher all cause-mortality rate over 12.2 years (HR 1.58, 95% CI 1.39–1.79).

High attenuation areas are associated with biomarkers of inflammation and extracellular matrix remodelling, reduced lung function, interstitial lung abnormalities, and a higher risk of death among community-dwelling adults.
Pathogen- and antibiotic-specific effects of prednisone in community-acquired pneumonia
Authors: Wirz Sebastian A. , Blum Claudine A. , Schuetz Philipp , Albrich Werner C. , Noppen Christoph , Mueller Beat , Christ-Crain Mirjam , Tarr Philip E.
Published: July 2016

In a double-blind, randomised, placebo-controlled trial of hospitalised patients with community-acquired pneumonia (CAP), we demonstrated shorter time to clinical stability (TTCS) with adjunct corticosteroid therapy compared with placebo.

We did a pre-planned, exploratory analysis of any association between microbiological diagnosis, antibiotic treatment and procalcitonin level and effect of prednisone on TTCS, mortality, and CAP complications (n=726 participants, enrolled between December 2009 and May 2014). Multiplex viral real time PCR was systematically performed in nasopharyngeal swabs beginning November 2011 (n=489). Other investigations and treatments were at the discretion of the physician. Effect modification was tested with inclusion of interaction terms in the statistical models.

Reduced TTCS with prednisone was seen in all microbiological, antibiotic, procalcitonin and afebrile patient subgroups. We found evidence for a different prednisone response in patients with pneumococcal pneumonia in whom intravenous antibiotic duration was not shorter (interaction p=0.01) with prednisone, as was observed in the remaining study population. In patients without macrolide treatment, rehospitalisations were not lower with prednisone (interaction p=0.04). After adjustment for multiple testing, these subgroup effects were no longer significant.

Prednisone was associated with shorter TTCS independent of CAP aetiology. In pneumococcal pneumonia, prednisone effects on secondary endpoints may be less favourable.
Efficacy of pirfenidone in patients with idiopathic pulmonary fibrosis with more preserved lung function
Authors: Albera Carlo , Costabel Ulrich , Fagan Elizabeth A. , Glassberg Marilyn K. , Gorina Eduard , Lancaster Lisa , Lederer David J. , Nathan Steven D. , Spirig Dominique , Swigris Jeff J.
Published: July 2016

Thispost hocanalysis examined the differences in idiopathic pulmonary fibrosis disease progression and the effects of pirfenidone in patients stratified by more preservedversusless preserved baseline lung function status using forced vital capacity (FVC) or GAP (gender, age and physiology) index stage.

Efficacy outcomes,i.e.FVC, 6-min walking distance (6MWD) and dyspnoea (University of California San Diego Shortness of Breath Questionnaire (UCSD SOBQ)), were analysed at 12 months in patients randomised to pirfenidone 2403 mg·day−1or placebo in the pooled phase 3 CAPACITY/ASCEND population (n=1247), with subgroups stratified by baseline FVC ≥80%versus<80% or GAP stage IversusII–III. Treatment-by-subgroup interaction was tested based on a rank ANCOVA model; factors in the model included study, region, treatment, subgroup and treatment-by-subgroup interaction term.

Patients with both more preserved (FVC ≥80% or GAP stage I) and less preserved (FVC <80% or GAP stage II–III) lung function at baseline demonstrated clinically significant disease progression at 12 months in terms of categorical decline in FVC, 6MWD and UCSD SOBQ. The magnitude of pirfenidone treatment effect was comparable between subgroups, regardless of whether lung function was classified using FVC or GAP index stage.

These findings support the initiation of treatment with pirfenidone, irrespective of stage of baseline lung function in this patient population.
Principles of practice parameters for the treatment of sleep disordered breathing in the elderly and frail elderly: the consensus of the International Geriatric Sleep Medicine Task Force
Authors: Netzer Nikolaus C. , Ancoli-Israel Sonia , Bliwise Donald L. , Fulda Stephany , Roffe Christine , Almeida Fernanda , Onen Hakki , Onen Fannie , Raschke Friedhart , Martinez Garcia Miguel Angel , Frohnhofen Helmut
Published: July 2016

Sleep disordered breathing (SDB) is a leading cause of morbidity worldwide. Its prevalence increases with age. Due to the demographic changes in industrial societies, pulmonologists and sleep physicians are confronted with a rapidly growing number of elderly SDB patients. For many physicians, it remains unclear how current guidelines for SDB management apply to elderly and frail elderly patients. The goal of this consensus statement is to provide guidance based on published evidence for SDB treatment in this specific patient group.

Clinicians and researchers with expertise in geriatric sleep medicine representing several countries were invited to participate in a task force. A literature search of PubMed from the past 12 years and a systematic review of evidence of studies deemed relevant was performed.

Recommendations for treatment management of elderly and frail elderly SDB patients based on published evidence were formulatedviadiscussion and consensus.

In the last 12 years, there have been surprisingly few studies examining treatment of SDB in older adults and even fewer in frail older adults. Studies that have been conducted on the management of SDB in the older patient population were rarely stratified for age. Studies in SDB treatment that did include age stratification mainly focused on middle-aged and younger patient groups. Based on the evidence that is available, this consensus statement highlights the treatment forms that can be recommended for elderly SDB patients and encourages treatment of SDB in this large patient group.
The relationship between body fat and respiratory function in young adults
Authors: Sutherland Tim J.T. , McLachlan Christene R. , Sears Malcolm R. , Poulton Richie , Hancox Robert J.
Published: July 2016

The relationship between adiposity and respiratory function is poorly understood. Most studies investigating this have used indirect measures of body fat and few have assessed how changes in adiposity influence lung function.

Body fat measured by bio-electrical impedance analysis, body mass index, waist circumference, spirometry, body plethysmography and transfer factor were measured at ages 32 and 38 years in 361 non-smoking, non-asthmatic participants from a population-based birth cohort.

Higher percentage body fat was associated with lower spirometric and plethysmographic lung volumes, but not with airflow obstruction, or transfer factor at 32 years. Changes in adiposity between ages 32 and 38 years were inversely associated with changes in lung volumes. These associations were generally stronger in men than women, but an association between increasing adiposity and lower airway function (forced expiratory volume in 1 s/forced vital capacity) was only found in women. Similar associations were found for body mass index and waist circumference.

Higher percentage body fat is associated with lower lung volumes. Direct and indirect measures of adiposity had similar associations with lung function. Adiposity had a greater effect on lung volumes in men than women but was associated with airway function only in women. There was little evidence that adiposity influenced transfer factor.
DISMISS: detection of stranded methylation in MeDIP-Seq data
Authors: Niazi Umar , Geyer Kathrin K. , Vickers Martin J. , Hoffmann Karl F. , Swain Martin T.
Published: July 2016

Background

DNA methylation is an important regulator of gene expression and chromatin structure. Methylated DNA immunoprecipitation sequencing (MeDIP-Seq) is commonly used to identify regions of DNA methylation in eukaryotic genomes. Within MeDIP-Seq libraries, methylated cytosines can be found in both double-stranded (symmetric) and single-stranded (asymmetric) genomic contexts. While symmetric CG methylation has been relatively well-studied, asymmetric methylation in any dinucleotide context has received less attention. Importantly, no currently available software for processing MeDIP-Seq reads is able to resolve these strand-specific DNA methylation signals. Here we introduce DISMISS, a new software package that detects strand-associated DNA methylation from existing MeDIP-Seq analyses.

Results

Using MeDIP-Seq datasets derived from Apis mellifera (honeybee), an invertebrate species that contains more asymmetric- than symmetric- DNA methylation, we demonstrate that DISMISS can identify strand-specific DNA methylation signals with similar accuracy as bisulfite sequencing (BS-Seq; single nucleotide resolution methodology). Specifically, DISMISS is able to confidently predict where DNA methylation predominates (plus or minus DNA strands – asymmetric DNA methylation; plus and minus DNA stands – symmetric DNA methylation) in MeDIP-Seq datasets derived from A. mellifera samples. When compared to DNA methylation data derived from BS-Seq analysis of A. mellifera worker larva, DISMISS-mediated identification of strand-specific methylated cytosines is 80 % accurate. Furthermore, DISMISS can correctly (p <0.0001) detect the origin (sense vs antisense DNA strands) of DNA methylation at splice site junctions in A. mellifera MeDIP-Seq datasets with a precision close to BS-Seq analysis. Finally, DISMISS-mediated identification of DNA methylation signals associated with upstream, exonic, intronic and downstream genomic loci from A. mellifera MeDIP-Seq datasets outperforms MACS2 (Model-based Analysis of ChIP-Seq2; a commonly used MeDIP-Seq analysis software) and closely approaches the results achieved by BS-Seq.

Conclusions

While asymmetric DNA methylation is increasingly being found in growing numbers of eukaryotic species and is the predominant pattern observed in some invertebrate genomes, it has been difficult to detect in MeDIP-Seq datasets using existing software. DISMISS now enables more sensitive examinations of MeDIP-Seq datasets and will be especially useful for the study of genomes containing either low levels of DNA methylation or for genomes containing relatively high amounts of asymmetric methylation.
TopoICSim: a new semantic similarity measure based on gene ontology
Authors: Ehsani Rezvan , Drabløs Finn
Published: July 2016

Background

The Gene Ontology (GO) is a dynamic, controlled vocabulary that describes the cellular function of genes and proteins according to tree major categories: biological process, molecular function and cellular component. It has become widely used in many bioinformatics applications for annotating genes and measuring their semantic similarity, rather than their sequence similarity. Generally speaking, semantic similarity measures involve the GO tree topology, information content of GO terms, or a combination of both.

Results

Here we present a new semantic similarity measure called TopoICSim (Topological Information Content Similarity) which uses information on the specific paths between GO terms based on the topology of the GO tree, and the distribution of information content along these paths. The TopoICSim algorithm was evaluated on two human benchmark datasets based on KEGG pathways and Pfam domains grouped as clans, using GO terms from either the biological process or molecular function. The performance of the TopoICSim measure compared favorably to five existing methods. Furthermore, the TopoICSim similarity was also tested on gene/protein sets defined by correlated gene expression, using three human datasets, and showed improved performance compared to two previously published similarity measures. Finally we used an online benchmarking resource which evaluates any similarity measure against a set of 11 similarity measures in three tests, using gene/protein sets based on sequence similarity, Pfam domains, and enzyme classifications. The results for TopoICSim showed improved performance relative to most of the measures included in the benchmarking, and in particular a very robust performance throughout the different tests.

Conclusions

The TopoICSim similarity measure provides a competitive method with robust performance for quantification of semantic similarity between genes and proteins based on GO annotations. An R script for TopoICSim is available at http://bigr.medisin.ntnu.no/tools/TopoICSim.R.
Effectiveness of percutaneous flexor tenotomies for the management and prevention of recurrence of diabetic toe ulcers: a systematic review
Authors: Scott Jennifer E. , Hendry Gordon J. , Locke John
Published: July 2016

Background

Diabetic toe ulcers are a potentially devastating complication of diabetes. In recent years, the percutaneous flexor tenotomy procedure for the correction of flexible claw and hammer‐toe contraction deformities has been proposed as a safe and effective technique for facilitating the healing of toe‐deformity related diabetic ulcers. The aim of this review is to critically appraise the evidence for the effectiveness of this surgical procedure in achieving ulcer healing, prevention of re‐ulceration, and to summarise the rate of post‐operative complications.

Method

A search of medical databases, was performed to locate relevant literature. Titles were screened prior to abstract and full text review to identify articles relevant to the research question. Search terms included truncations of “tenotomy”, “toe”, “hallux”, “digit”, “diabetes” and “ulcer”. Peer reviewed primary research study designs specified as suitable for systematic reviews by the Centre for Reviews and Dissemination were included. Studies were excluded if they used a concurrent secondary procedure or included non‐diabetic patients without reporting outcomes separately. Included studies were appraised for quality using the Methodological Index for Non‐Randomised Studies tool. Levels of evidence were subsequently assigned to each outcome of interest (healing rate and prevention of re‐ulceration).

Results

From a total search yield of 42 articles, 5 eligible studies (all case series designs) were identified for inclusion. Included studies were of low‐to‐moderate methodological quality when assessed using the MINORS tool. A total of 250 flexor tenotomy procedures were performed in a total of 163 patients. Included studies generally reported good healing rates (92–100 % within 2 months) post‐op follow‐up), relatively few recurrences (0–18 % at 22 months median post‐op follow‐up), and low incidences of infection or new deformity. Transfer ulcers developing on adjacent areas as a result of shifted pressure were reported by several authors.

The validity of these results is undermined by methodological limitations inherent to case series designs such as a lack of control groups, non‐randomised designs, as well as inconsistent reporting of post‐intervention follow‐up periods. There was level 4 evidence for the flexor tenotomy procedure in facilitating ulcer healing and preventing re‐ulceration.

Conclusion

More definitive research evidence is needed in this area to determine whether or not the flexor tenotomy is a safe and effective treatment option for people with, or at risk of developing diabetic toe ulcers. Whilst the available literature reports that the procedure may be associated with high healing rates, relatively low recurrence rates and low incidences of post‐op complications, methodological limitations restrict the value of these findings.
Direct conversion of mouse embryonic fibroblasts into functional keratinocytes through transient expression of pluripotency-related genes
Authors: Iacovides Demetris , Rizki Gizem , Lapathitis Georgios , Strati Katerina
Published: July 2016

The insufficient ability of specialized cells such as neurons, cardiac myocytes, and epidermal cells to regenerate after tissue damage poses a great challenge to treat devastating injuries and ailments. Recent studies demonstrated that a diverse array of cell types can be directly derived from embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), or somatic cells by combinations of specific factors. The use of iPSCs and direct somatic cell fate conversion, or transdifferentiation, holds great promise for regenerative medicine as these techniques may circumvent obstacles related to immunological rejection and ethical considerations. However, producing iPSC-derived keratinocytes requires a lengthy two-step process of initially generating iPSCs and subsequently differentiating into skin cells, thereby elevating the risk of cellular damage accumulation and tumor formation. In this study, we describe the reprogramming of mouse embryonic fibroblasts into functional keratinocytes via the transient expression of pluripotency factors coupled with directed differentiation. The isolation of an iPSC intermediate is dispensable when using this method. Cells derived with this approach, termed induced keratinocytes (iKCs), morphologically resemble primary keratinocytes. Furthermore they express keratinocyte-specific markers, downregulate mesenchymal markers as well as the pluripotency factors Oct4, Sox2, and Klf4, and they show important functional characteristics of primary keratinocytes. iKCs can be further differentiated by high calcium administration in vitro and are capable of regenerating a fully stratified epidermis in vivo. Efficient conversion of somatic cells into keratinocytes could have important implications for studying genetic skin diseases and designing regenerative therapies to ameliorate devastating skin conditions.
Some fixed point results via R-functions
Authors: Nastasi Antonella , Vetro Pasquale , Radenović Stojan
Published: July 2016

We establish existence and uniqueness of fixed points for a new class of mappings, by using R-functions and lower semi-continuous functions in the setting of metric spaces. As consequences of this results, we obtain several known fixed point results, in metric and partial metric spaces. An example is given to support the new theory. A homotopy result for operators on a set endowed with a metric is given as application.
Partial epithelial-mesenchymal transition in keloid scars: regulation of keloid keratinocyte gene expression by transforming growth factor-β1
Authors: Hahn Jennifer M. , McFarland Kevin L. , Combs Kelly A. , Supp Dorothy M.
Published: July 2016

Background

Keloids are an extreme form of abnormal scarring that result from a pathological fibroproliferative wound healing process. The molecular mechanisms driving keloid pathology remain incompletely understood, hindering development of targeted, effective therapies. Recent studies in our laboratory demonstrated that keloid keratinocytes exhibit adhesion abnormalities and display a transcriptional signature reminiscent of cells undergoing epithelial-mesenchymal transition (EMT), suggesting a role for EMT in keloid pathology. In the current study, we further define the EMT-like phenotype of keloid scars and investigate regulation of EMT-related genes in keloid.

Methods

Primary keratinocytes from keloid scar and normal skin were cultured in the presence or absence of transforming growth factor beta 1 (TGF-β1) +/− inhibitors of TGF-β1 and downstream signaling pathways. Gene expression was measured using quantitative polymerase chain reaction. Migration was analyzed using an in vitro wound healing assay. Proteins in keloid scar and normal skin sections were localized by immunohistochemistry. Statistical analyses utilized SigmaPlot (SyStat Software, San Jose, CA) or SAS® (SAS Institute, Cary, NC).

Results

In keloid and normal keratinocytes, TGF-β1 regulated expression of EMT-related genes, including hyaluronan synthase 2, vimentin, cadherin-11, wingless-type MMTV integration site family, member 5A, frizzled 7, ADAM metallopeptidase domain 19, and interleukin-6. Inhibition of canonical TGF-β1 signaling in keloid keratinocytes significantly inhibited expression of these genes, and TGF-β1 stimulation of normal keratinocytes increased their expression. The inhibition of the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway or the p38 mitogen-activated protein kinase pathway attenuated TGF-β1-induced expression of subsets of these genes. Migration of keloid keratinocytes, previously shown to be increased compared with normal keratinocytes, was significantly reduced by inhibition of TGF-β1 or ERK1/2 signaling. Biomarkers of EMT, including reduced E-cadherin and increased active β-catenin, were observed in keloid epidermis in vivo. However, evidence of basement membrane breakdown in keloid scar was not observed.

Conclusions

The results suggest that keloid keratinocytes exist in an EMT-like metastable state, similar to activated keratinocytes in healing wounds. The EMT-like gene expression pattern of keloid keratinocytes is regulated by canonical and non-canonical TGF-β1 signaling pathways. Therefore, interventions targeting TGF-β1-regulated EMT-like gene expression in keloid keratinocytes may serve to suppress keloid scarring.
The elastic anisotropy of clay minerals
Authors: Sayers Colin M. , den Boer Lennert D.
Published: July 2016

The layered structure of clay minerals produces large elastic anisotropy due to the presence of strong covalent bonds within layers and weaker electrostatic bonds in between. Technical difficulties associated with small grain size preclude experimental measurement of single-crystal elastic moduli. However, theoretical calculations of the complete elastic tensors of several clay minerals have been reported, using either first-principle calculations based on density functional theory or molecular dynamics. Because of the layered microstructure, the elastic stiffness tensor obtained from such calculations can be approximated to good accuracy as a transversely isotropic (TI) medium. The TI-equivalent elastic moduli of clay minerals indicate that Thomsen’s anisotropy parameters [Formula: see text] and [Formula: see text] are large and positive, whereas [Formula: see text] is small or negative. A least-squares inversion for the elastic properties of a best-fitting equivalent TI medium consisting of two isotropic layers to the elastic properties of clay minerals indicates that the shear modulus of the stiffest layer is considerably larger than the softest layer, consistent with the expected high compliance of the interlayer region in clay minerals. It is anticipated that the elastic anisotropy parameters derived from the best-fitting TI approximation to the elastic stiffness tensor of clay minerals will find applications in rock physics for seismic imaging, amplitude variation with offset analysis, and geomechanics.
Induced polarization and pore radius — A discussion
Authors: Weller Andreas , Zhang Zeyu , Slater Lee , Kruschwitz Sabine , Halisch Matthias
Published: July 2016

Permeability estimation from induced polarization (IP) measurements is based on a fundamental premise that the characteristic relaxation time [Formula: see text] is related to the effective hydraulic radius [Formula: see text] controlling fluid flow. The approach requires a reliable estimate of the diffusion coefficient of the ions in the electrical double layer. Others have assumed a value for the diffusion coefficient, or postulated different values for clay versus clay-free rocks. We have examined the link between a widely used single estimate of [Formula: see text] and [Formula: see text] for an extensive database of sandstone samples, in which mercury porosimetry data confirm that [Formula: see text] is reliably determined from a modification of the Hagen-Poiseuille equation assuming that the electrical tortuosity is equal to the hydraulic tortuosity. Our database does not support the existence of one or two distinct representative diffusion coefficients but instead demonstrates strong evidence for six orders of magnitude of variation in an apparent diffusion coefficient that is well-correlated with [Formula: see text] and the specific surface area per unit pore volume [Formula: see text]. Two scenarios can explain our findings: (1) the length scale defined by [Formula: see text] is not equal to [Formula: see text] and is likely much longer due to the control of pore-surface roughness or (2) the range of diffusion coefficients is large and likely determined by the relative proportions of the different minerals (e.g., silica and clays) making up the rock. In either case, the estimation of [Formula: see text] (and hence permeability) is inherently uncertain from a single characteristic IP relaxation time as considered in this study.
Protein synthesis and degradation are essential to regulate germline stem cell homeostasis in Drosophila testes
Authors: Yu Jun , Lan Xiang , Chen Xia , Yu Chao , Xu Yiwen , Liu Yujuan , Xu Lingna , Fan Heng-Yu , Tong Chao
Published: July 2016

The homeostasis of self-renewal and differentiation in stem cells is controlled by intrinsic signals and their niche. We conducted a large-scale RNA interference (RNAi) screen in Drosophila testes and identified 221 genes required for germline stem cell (GSC) maintenance or differentiation. Knockdown of these genes in transit-amplifying spermatogonia and cyst cells further revealed various phenotypes. Complex analysis uncovered that many of the identified genes are involved in key steps of protein synthesis and degradation. A group of genes that are required for mRNA splicing and protein translation contributes to both GSC self-renewal and early germ cell differentiation. Loss of genes in the protein degradation pathway in cyst cells leads to testis tumors consisting of overproliferated germ cells. Importantly, in the Cullin 4-RING E3 ubiquitin ligase (CRL4) complex, we identified multiple proteins that are crucial to GSC self-renewal: pic/DDB1, a CRL4 linker protein, is not only required for GSC self-renewal in flies but also for maintenance of spermatogonial stem cells (SSCs) in mice.
Live imaging of X chromosome reactivation dynamics in early mouse development can discriminate naïve from primed pluripotent stem cells
Authors: Kobayashi Shin , Hosoi Yusuke , Shiura Hirosuke , Yamagata Kazuo , Takahashi Saori , Fujihara Yoshitaka , Kohda Takashi , Okabe Masaru , Ishino Fumitoshi
Published: July 2016

Pluripotent stem cells can be classified into two distinct states, naïve and primed, which show different degrees of potency. One difficulty in stem cell research is the inability to distinguish these states in live cells. Studies on female mice have shown that reactivation of inactive X chromosomes occurs in the naïve state, while one of the X chromosomes is inactivated in the primed state. Therefore, we aimed to distinguish the two states by monitoring X chromosome reactivation. Thus far, X chromosome reactivation has been analysed using fixed cells; here, we inserted different fluorescent reporter gene cassettes (mCherry and eGFP) into each X chromosome. Using these knock-in ‘Momiji’ mice, we detected X chromosome reactivation accurately in live embryos, and confirmed that the pluripotent states of embryos were stable ex vivo, as represented by embryonic and epiblast stem cells in terms of X chromosome reactivation. Thus, Momiji mice provide a simple and accurate method for identifying stem cell status based on X chromosome reactivation.
Effects of elevated pCO2 and feeding on net calcification and energy budget of the Mediterranean cold-water coral Madrepora oculata
Authors: Maier C. , Popp P. , Sollfrank N. , Weinbauer M. G. , Wild C. , Gattuso J.-P.
Published: July 2016

Ocean acidification is a major threat to calcifying marine organisms such as deep-sea cold-water corals (CWC), but related knowledge is scarce. The aragonite saturation threshold (Ωa) for calcification, respiration, and organic matter fluxes was investigated experimentally in the Mediterranean Madrepora oculata (Linnaeus 1758). Over 10 weeks, colonies were maintained under two feeding regimes (uptake of 36.75 and 7.46 µmol C polyp−1 week−1) and exposed in 2 week intervals to a consecutively changing air-CO2 mix (pCO2) of 400, 1600, 800, 2000 and 400 ppm. There was a significant effect of feeding on calcification at initial ambient pCO2, while at consecutive pCO2 treatments feeding had no effect on calcification. Respiration was not significantly affected by feeding or pCO2 levels. Coral skeletons started to dissolve at an average Ωa threshold of 0.92, but recovered and started to calcify again at Ωa≥1. The surplus energy required to counteract dissolution at elevated pCO2 (≥1600µatm) was twice that at ambient pCO2. Yet, feeding had no mitigating effect at increasing pCO2 levels. This could be due to the fact that the energy required for calcification is a small fraction (1 to 3%) of the total metabolic energy demand and corals even under low food conditions might therefore still be able to allocate this small portion of energy to calcification. The response and resistance to ocean acidification is consequently not controlled by feeding in this species, but more likely by chemical reaction at the site of calcification and exchange processes between the calicoblastic layer and ambient seawater.
Experimental tests of planar strain theory for predicting bone cross-sectional longitudinal and shear strains
Authors: Verner Kari A. , Lehner Michael , Lamas Luis P. , Main Russell P.
Published: July 2016

Understanding the diversity of skeletal loading regimes in vertebrate long bones during locomotion has been significantly enhanced by the application of planar strain theory (PST) to in vivo bone strain data. PST is used to model the distribution of longitudinal strains normal to the bone's transverse cross-section and the location of the neutral axis of bending. To our knowledge, the application of this theory to skeletal biomechanics has not been experimentally validated. We evaluated the accuracy of PST using strain measurements from emu tibiotarsi instrumented with four strain gauges and loaded in ex vivo four-point bending. Using measured strains from three-gauge combinations, PST was applied to predict strain values at a fourth gauge's location. Experimentally measured and predicted strain values correlated linearly with a slope near 1.0, suggesting that PST accurately predicts longitudinal strains. Additionally, we assessed the use of PST to extrapolate shear strains to locations on a bone not instrumented with rosette strain gauges. Guineafowl TBTs were instrumented with rosette strain gauges and in vivo longitudinal and shear strains were measured during treadmill running. Individual-specific and sample-mean ratios between measured longitudinal strains from the medial and posterior bone surfaces were used to extrapolate posterior-site shear strain from shear strains measured on the medial surface. Measured and predicted shear strains at the posterior gauge site using either ratio showed trends for a positive correlation between measured and predicted strains, but the correlation did not equal 1.0 and had a non-zero intercept, suggesting that the use of PST should be carefully considered in the context of the goals of the study and the desired precision for the predicted shear strains.
Flowing water affects fish fast-starts: escape performance of the Hawaiian stream goby,Sicyopterus stimpsoni
Authors: Diamond Kelly M. , Schoenfuss Heiko L. , Walker Jeffrey A. , Blob Richard W.
Published: July 2016

Experimental measurements of escape performance in fishes have typically been conducted in still water; however, many fishes inhabit environments with flow that could impact escape behavior. We examined the influences of flow and predator attack direction on the escape behavior of fish, using juveniles of the amphidromous Hawaiian goby Sicyopterus stimpsoni. In nature, these fish must escape ambush predation while moving through streams with high-velocity flow. We measured the escape performance of juvenile gobies while exposing them to a range of water velocities encountered in natural streams and stimulating fish from three different directions. Frequency of response failure across treatments indicated strong effects of flow conditions and attack direction. Juvenile S. stimpsoni had uniformly high response rates for attacks from a caudal direction (opposite flow); however, response rates for attacks from a cranial direction (matching flow) decreased dramatically as flow speed increased. Mechanical stimuli produced by predators attacking in the same direction as flow might be masked by the flow environment, impairing the ability of prey to detect attacks. Thus, the likelihood of successful escape performance in fishes can depend critically on environmental context.
Acclimation potential of Arctic cod (Boreogadus saida Lepechin) from the rapidly warming Arctic Ocean
Authors: Drost H. E. , Lo M. , Carmack E. C. , Farrell A. P.
Published: July 2016

In consequence of the growing concern with warming of the Arctic Ocean, this study quantified the thermal acclimation responses of Boreogadus saida, a key Arctic food web fish. Physiological rates for cardio-respiratory functions as well as critical maximum temperature (Tcmax) for loss of equilibrium (LOE) were measured. The transition temperatures for these functions (LOE, the rate of oxygen uptake and maximum heart rate) during acute warming were used to gauge phenotypic plasticity after thermal acclimation from 0.5°C up to 6.5°C for 1 month (respiratory and Tcmax measurements) and 6 months (cardiac measurements). Tcmax increased significantly by 2.3°C from 14.9°C to 17.1°C with thermal acclimation, while the optimum temperature for absolute aerobic scope increased by 4.5°C over the same range of thermal acclimation. Warm acclimation reset the maximum heart rate to a statistically lower rate, but the first Arrhenius breakpoint temperature during acute warming was unchanged. The hierarchy of transition temperatures were quantified at three acclimation temperatures and were fitted inside a Fry temperature tolerance polygon to better define ecologically relevant thermal limits to performance of B. saida. We conclude that B. saida can acclimate to 6.5°C water temperatures in the laboratory. However, at this acclimation temperature 50% of the fish were unable to recover from maximum swimming at the 8.5°C test temperature and their cardio-respiratory performance started to decline at water temperatures greater than 5.4°C. Such costs in performance may limit the ecological significance of B. saida acclimation potential.
Evaluating the role of NRF-1 in regulation of the goldfish COX4-1 gene in response to temperature
Authors: Gao Ge , Moyes Christopher D.
Published: July 2016

Cold acclimation in fish typically increases muscle mitochondrial enzymes. In mammals, stressors that increase mitochondrial content are mediated though transcriptional regulators, including nuclear respiratory factor-1 (NRF-1). Focusing on the goldfish gene for cytochrome c oxidase (COX) subunit 4-1, we analyzed the regulatory regions in various contexts to identify a mechanistic link between NRF-1 and cold-induced mitochondrial proliferation. Promoter analysis implicated two putative NRF-1 sites: one in the proximal promoter and a second in exon 1, which encodes the 5′ untranslated region (5′-UTR). Transfection into mouse myoblasts showed that deletion of a region that included the proximal NRF-1 site reduced promoter activity by 30%, however mutagenesis of the specific sequence had no effect. Thermal sensitivity analyses performed in rainbow trout gonadal fibroblasts (RTG-2) showed no effect of temperature (4 vs. 19°C) on reporter gene expression. Likewise, reporters injected into muscle of thermally-acclimated goldfish (4 vs. 26°C) showed no elevation in expression. There was no difference in thermal responses of COX4-1 promoter reporters constructed from homologous regions of eurythermal goldfish and stenothermal zebrafish genes. NRF-1 chromatin immunoprecipitation of thermally acclimated goldfish muscle showed no temperature effect on NRF-1 binding to either the proximal promoter or 5′-UTR. It remains possible that the cold-induced up-regulation of COX4-1 expression is a result of NRF-1 binding to distal regulatory regions or through indirect effects on other transcription factors. However, the proximal promoter does not appear to play a role in mediating the thermal response of the COX4-1 gene in fish.
Insulin effects on honeybee appetitive behaviour
Authors: Goñalons Carolina Mengoni , Guiraud Marie , Sanchez María Gabriela de Brito , Farina Walter M.
Published: July 2016

Worker honeybees (Apis mellifera L.) carry out multiple tasks throughout their adult lifespan. It has been suggested that the insulin/insulin-like signalling pathway participates in regulating behavioural maturation in eusocial insects. Insulin signalling increases as the honeybee worker transitions from nurse to food processor to forager. As behavioural shifts require differential usage of sensory modalities, our aim was to assess insulin effects on olfactory and gustatory responsiveness as well as on olfactory learning in preforaging honeybee workers of different ages. Adults were reared in the laboratory or in the hive. Immediately after being injected with insulin or vehicle (control), and focussing on the proboscis extension response, bees were tested for their spontaneous response to odours, sucrose responsiveness and ability to discriminate odours through olfactory conditioning. Bees injected with insulin have higher spontaneous odour responses. Sucrose responsiveness and odour discrimination are differentially affected by treatment according to age; whereas insulin increases gustatory responsiveness and diminishes learning abilities of younger workers, it has the opposite effect on older bees. As a summary, insulin can improve chemosensory responsiveness in young workers, but also worsens their learning abilities to discriminate odours. The insulin signalling pathway is responsive in young workers, although they are not yet initiating outdoor activities. Our results show strong age dependent effects of insulin on appetitive behaviour, which uncover differences in insulin signalling regulation throughout the honeybee worker's adulthood.
Long-Term Care Insurance Decisions
Authors: Bodily Samuel E. , Furman Bryan
Published: July 2016

The purchase of long-term care (LTC) insurance is a difficult lifetime choice made in the face of highly uncertain risks, including mortality, morbidity, timing and length of LTC, and portfolio investment risk. Many individuals do not know how to think about this decision properly and, in the face of too much anecdotal and too little objective information, will not proactively decide. We used Monte Carlo simulation modeling with detailed, experience-based distributions for LTC uncertainties and their correlations to project investment growth to death given alternative levels of LTC insurance. Using constant risk aversion, we calculate certainty equivalents for the resulting distributions of final holdings at death. Decisions were separated for male and female individuals and group and individual market insurance opportunities. Sensitivity analysis was conducted varying age, cost of coverage, starting investment amount, risk tolerance, return on portfolio investment, inflation, and length of LTC coverage. Optimality results suggest low levels of coverage or no insurance, with higher use of insurance only for individuals who are young, have low risk tolerance, low starting portfolio amounts, or combinations of these characteristics. While the contribution of this work is to assist individual decision making, it will also be informative to policy makers and insurance companies.
Modification and Validation of the Triglyceride-to–HDL Cholesterol Ratio as a Surrogate of Insulin Sensitivity in White Juveniles and Adults without Diabetes Mellitus: The Single Point Insulin Sensitivity Estimator (SPISE)
Authors: Paulmichl Katharina , Hatunic Mensud , Højlund Kurt , Jotic Aleksandra , Krebs Michael , Mitrakou Asimina , Porcellati Francesca , Tura Andrea , Bergsten Peter , Forslund Anders , Manell Hannes , Widhalm Kurt , Weghuber Daniel , Anderwald Christian-Heinz ,   the Beta-JUDO Investigators
Published: July 2016

BACKGROUND

The triglyceride-to–HDL cholesterol (TG/HDL-C) ratio was introduced as a tool to estimate insulin resistance, because circulating lipid measurements are available in routine settings. Insulin, C-peptide, and free fatty acids are components of other insulin-sensitivity indices but their measurement is expensive. Easier and more affordable tools are of interest for both pediatric and adult patients.

METHODS

Study participants from the Relationship Between Insulin Sensitivity and Cardiovascular Disease [43.9 (8.3) years, n = 1260] as well as the Beta-Cell Function in Juvenile Diabetes and Obesity study cohorts [15 (1.9) years, n = 29] underwent oral-glucose-tolerance tests and euglycemic clamp tests for estimation of whole-body insulin sensitivity and calculation of insulin sensitivity indices. To refine the TG/HDL ratio, mathematical modeling was applied including body mass index (BMI), fasting TG, and HDL cholesterol and compared to the clamp-derived M-value as an estimate of insulin sensitivity. Each modeling result was scored by identifying insulin resistance and correlation coefficient. The Single Point Insulin Sensitivity Estimator (SPISE) was compared to traditional insulin sensitivity indices using area under the ROC curve (aROC) analysis and χ2 test.

RESULTS

The novel formula for SPISE was computed as follows: SPISE = 600 × HDL-C0.185/(TG0.2 × BMI1.338), with fasting HDL-C (mg/dL), fasting TG concentrations (mg/dL), and BMI (kg/m2). A cutoff value of 6.61 corresponds to an M-value smaller than 4.7 mg · kg−1 · min−1 (aROC, M:0.797). SPISE showed a significantly better aROC than the TG/HDL-C ratio. SPISE aROC was comparable to the Matsuda ISI (insulin sensitivity index) and equal to the QUICKI (quantitative insulin sensitivity check index) and HOMA-IR (homeostasis model assessment–insulin resistance) when calculated with M-values.

CONCLUSIONS

The SPISE seems well suited to surrogate whole-body insulin sensitivity from inexpensive fasting single-point blood draw and BMI in white adolescents and adults.
Application of empirical mode decomposition method for characterization of random vibration signals
Authors: Parman Setyamartana , Yazid Edwar
Published: July 2016

Characterization of finite measured signals is a great of importance in dynamical modeling and system identification. This paper addresses an approach for characterization of measured random vibration signals where the approach rests on a method called empirical mode decomposition (EMD). The applicability of proposed approach is tested in one numerical and experimental data from a structural system, namely spar platform. The results are three main signal components, comprising: noise embedded in the measured signal as the first component, first intrinsic mode function (IMF) called as the wave frequency response (WFR) as the second component and second IMF called as the low frequency response (LFR) as the third component while the residue is the trend. Band-pass filter (BPF) method is taken as benchmark for the results obtained from EMD method.
Review on the application of physiological and biomechanical measurement methods in driving fatigue detection
Authors: Sanjaya Kadek Heri , Lee Soomin , Katsuura Tetsuo
Published: July 2016

Previous studies have identified driving fatigue as the main cause of road traffic accidents, therefore, the aim of this literature review is to explore the characteristics of driving fatigue both physically and mentally as well as to explore the technology available to measure the process of fatigue physiologically. We performed e-searching in the field of fatigue detection methods through keywords tracking. The instruments studied have their own strength and weakness, and some are intrusive while the others are non-intrusive. The accuracy and stability of measurements are also varied between those instruments. In order to create more reliable fatigue detection methods, it is necessary to involve more instruments with an inter-disciplinary approach. Our intention is to make this study as a stepping stone for a more comprehensive in-vehicle real-time man-machine interaction study. Such study will not only be useful to prevent traffic accidents but also to bridge man and machine communication in the vehicle control along with developing newer technology in the field of vehicle automation.
Optimized object tracking technique using Kalman filter
Authors: Taylor Liana Ellen , Mirdanies Midriem , Saputra Roni Permana
Published: July 2016

This paper focused on the design of an optimized object tracking technique which would minimize the processing time required in the object detection process while maintaining accuracy in detecting the desired moving object in a cluttered scene. A Kalman filter based cropped image is used for the image detection process as the processing time is significantly less to detect the object when a search window is used that is smaller than the entire video frame. This technique was tested with various sizes of the window in the cropping process. MATLAB® was used to design and test the proposed method. This paper found that using a cropped image with 2.16 multiplied by the largest dimension of the object resulted in significantly faster processing time while still providing a high success rate of detection and a detected center of the object that was reasonably close to the actual center.
Registration-based Mapping of Aboveground Disparities (RMAD) for Building Detection in Off-nadir VHR Stereo Satellite Imagery
Authors: Suliman Alaeldin , Zhang Yun , Al-Tahir Raid
Published: July 2016

Reliable building delineation in very high resolution (VHR) satellite imagery can be achieved by precise disparity information extracted from stereo pairs. However, off-nadir VHR images over urban areas contain many occlusions due to building leaning that creates gaps in the extracted
disparity maps. The typical approach to fill these gaps is by interpolation. However, it inevitably degrades the quality of the disparity map and reduces the accuracy of building detection. Thus, this research proposes a registration-based technique for mapping the disparity of off-terrain
objects to avoid the need for disparity interpolation and normalization. The generated disparity by the proposed technique is then used to support building detection in off-nadir VHR satellite images. Experiments in a high-rise building area confirmed that 75 percent of the detected building
roofs overlap precisely the reference data, with almost 100 percent correct detection. These accuracies are substantially higher than those achieved by other published research.