bluuebunny/crossref_metadata_2025 huggingface dataset:
Global Sea Surface Temperature Forecasts Using an Improved Multimodel Approach
Authors: Kaiser Khan Mohammad Zaved , Mehrotra Rajeshwar , Sharma Ashish , Sankarasubramanian A.
Published: February 2014

With the availability of hindcasts or real-time forecasts from a number of coupled climate models, multimodel ensemble forecasting systems have gained popularity in recent years. However, many models share similar physics or modeling processes, which may lead to similar (or strongly correlated) forecasts. Assigning equal weights to each model in space and time may result in a biased forecast with narrower confidence limits than is appropriate. Although methods for combining forecasts that take into consideration differences in model accuracy over space and time exist, they suffer from a lack of consideration of the intermodel dependence that may exist. This study proposes an approach that considers the dependence among models while combining multimodel ensemble forecast. The approach is evaluated by combining sea surface temperature (SST) forecasts from five climate models for the period 1960–2005. The variable of interest, the monthly global sea surface temperature anomalies (SSTA) at a 5° × 5° latitude–longitude grid, is predicted three months in advance using the proposed algorithm. Results indicate that the proposed approach offers consistent and significant improvements for all the seasons over the majority of grid points compared to the case in which the dependence among the models is ignored. Consequently, the proposed approach of combining multiple models, taking into account the interdependence that exists, provides an attractive strategy to develop improved SST forecasts.
Evaluation of the New Version of the Laser-Optical Disdrometer, OTT Parsivel2
Authors: Tokay Ali , Wolff David B. , Petersen Walter A.
Published: February 2014

A comparative study of raindrop size distribution measurements has been conducted at NASA’s Goddard Space Flight Center where the focus was to evaluate the performance of the upgraded laser-optical OTT Particle Size Velocity (Parsivel2; P2) disdrometer. The experimental setup included a collocated pair of tipping-bucket rain gauges, OTT Parsivel (P1) and P2 disdrometers, and Joss–Waldvogel (JW) disdrometers. Excellent agreement between the two collocated rain gauges enabled their use as a relative reference for event rain totals. A comparison of event total showed that the P2 had a 6% absolute bias with respect to the reference gauges, considerably lower than the P1 and JW disdrometers. Good agreement was also evident between the JW and P2 in hourly raindrop spectra for drop diameters between 0.5 and 4 mm. The P2 drop concentrations mostly increased toward small sizes, and the peak concentrations were mostly observed in the first three measurable size bins. The P1, on the other hand, underestimated small drops and overestimated the large drops, particularly in heavy rain rates. From the analysis performed, it appears that the P2 is an improvement over the P1 model for both drop size and rainfall measurements. P2 mean fall velocities follow accepted terminal fall speed relationships at drop sizes less than 1 mm. As a caveat, the P2 had approximately 1 m s−1 slower mean fall speed with respect to the terminal fall speed near 1 mm, and the difference between the mean measured and terminal fall speeds reduced with increasing drop size. This caveat was recognized as a software bug by the manufacturer and is currently being investigated.
On the Choice of an Optimal Localization Radius in Ensemble Kalman Filter Methods
Authors: Kirchgessner Paul , Nerger Lars , Bunse-Gerstner Angelika
Published: February 2014

In data assimilation applications using ensemble Kalman filter methods, localization is necessary to make the method work with high-dimensional geophysical models. For ensemble square root Kalman filters, domain localization (DL) and observation localization (OL) are commonly used. Depending on the localization method, appropriate values have to be chosen for the localization parameters, such as the localization length and the weight function. Although frequently used, the properties of the localization techniques are not fully investigated. Thus, up to now an optimal choice for these parameters is a priori unknown and they are generally found by expensive numerical experiments. In this study, the relationship between the localization length and the ensemble size in DL and OL is studied using twin experiments with the Lorenz-96 model and a two-dimensional shallow-water model. For both models, it is found that the optimal localization length for DL and OL depends linearly on an effective local observation dimension that is given by the sum of the observation weights. In the experiments no influence of the model dynamics on the optimal localization length was observed. The effective observation dimension defines the degrees of freedom that are required for assimilating observations, while the ensemble size defines the available degrees of freedom. Setting the localization radius such that the effective local observation dimension equals the ensemble size yields an adaptive localization radius. Its performance is tested using a global ocean model. The experiments show that the analysis quality using the adaptive localization is similar to the analysis quality of an optimally tuned constant localization radius.
Intra-Regional Trade and Sectoral Performances
Authors: Oguanobi Chibuike R. , Akamobi Anthony A. , Nzeribe Geraldine E. , Aniebo Chibueze A. , Chukwuma Ogochukwu T.
Published: February 2014

This article examined whether Nigeria’s major sectors, that is, manufacturing, agricultural, oil and services have responded significantly to trade between the country and other Economic Community of West African States (ECOWAS) countries. Outputs of these sectors were used as their measures while intra-regional trade was captured using Nigeria’s export to and imports from the rest of ECOWAS. Using data for the period 1996 to 2008 and employing (vector autoregression) VAR methodology, the impulse response functions show that the country’s services sector had a significant positive response to her intra-regional import and export. Agricultural sector conversely had a significant negative response to import. Oil sector responded significantly to export up to midway into our sample space. But generally, Nigerian sectors have not responded significantly to intra-ECOWAS trade. Based on this finding, we therefore recommend that ECOWAS authorities should ensure comprehensive implementation of the region’s trade liberalization scheme (ETLS). This will enhance trade within the region.
Narrative magic: Stories and the ways of desire
Authors: Belsey Catherine
Published: February 2014

Fictions that include an account of how stories are received show narrative as enlisting the desire of the reader or hearer. While fiction demonstrates what the magic of the signifier can do to allay desire when language is set free from reality, in the end narratives withhold satisfaction of the desire they engender, since the worlds they create must eventually be relinquished. To that degree, narrative fiction brings to light the condition of the speaking being as Lacanian psychoanalysis conceives it, at once empowered and deprived by access to language, and in quest of a presence language cannot deliver. In so far as they are ungrounded, stories are able to exceed cultural orthodoxies, conjuring into being desired possibilities, aspirations, and corollary fears. Supplementary in that sense and dangerous, in consequence, to the orthodoxies they supplement, fictional narratives can therefore bring to light the inadequacy of customary assumptions. Located in time, stories offer a knowledge – of cultural difference, as well as of the laws of desire that underlie it.
Just what is narrative urgency?
Authors: Simpson Paul
Published: February 2014

This article takes as its main point of departure a body of empirical research on reading and text processing, and makes particular reference to the type of experiments conducted in Egidi and Gerrig (2006) and Rapp and Gerrig (2006). Broadly put, these experiments (i) explore the psychology of readers’ preferences for narrative outcomes, (ii) examine the way readers react to characters’ goals and actions, and (iii) investigate how readers tend to identify with characters’ goals the more ‘urgently’ those goals are narrated.

The present article signals how stylistics can productively enrich such experimental work. Stylistics, it is argued, is well equipped to deal with subtle and nuanced variations in textual patterns without losing sight of the broader cognitive and discoursal positioning of readers in relation to these patterns. Making particular reference to what might constitute narrative ‘urgency’, the article develops a model which amalgamates different strands of contemporary research in narrative stylistics. This model advances and elaborates three key components: a Stylistic Profile, a Burlesque Block and a Kuleshov Monitor. Developing analyses of, and informal informant tests on, examples of both fiction and film, the article calls for a more rounded and sophisticated understanding of style in empirical research on subjects’ responses to patterns in narrative.
Voice, tone, and the rhetoric of narrative communication
Authors: Phelan James
Published: February 2014

The essay argues for a rhetorical view of narrative communication as an author’s deployment of particular resources in order to generate certain responses in readers, and then examines the nature and possible functions of voice as a resource. It defines voice as the synthesis of style (diction and syntax), tone (a speaker’s attitude toward an utterance) and values (ideological and ethical), and then turns to analyzing the role of voice—and more particularly, the role of tone—in narrative communication. With George V Higgins’s The Friends of Eddie Coyle as Exhibit A, the essay examines the functions of voice and tone in fictional dialogue, and with Joan Didion’s The Year of Magical Thinking as Exhibit B, it examines their role in nonfictional narration. The essay concludes with a call for further analyses of voice and tone, even as it cautions that their roles may be more or less important as we move from one narrative to another.
The Information Content of Alternate Implied Volatility Models: Case of Indian Markets
Authors: Kumar A. Vinay , Jaiswal Shikha
Published: February 2014

The information content to forecast the future realised volatility by model-based implied volatility and model free implied volatility has been an increasingly important area of research. There is a lot of literature suggesting that Black Scholes implied volatility is an efficient estimator ( Fleming 1998 ); on the contrary there are studies suggesting that model free measures like VIX could be more informative ( Jiang and Tian 2005 ). There is also a view, as evidenced in the earlier research, that there is a complete lack of relationship between them. The current study seeks to understand these dynamics in the Indian context and add to the debate by specifying market direction variables which could explain the relationship. The study tries to bring out the short-term relationship between the two volatilities. The present study finds evidence supporting Fleming ( 1998 ) and contrary to the evidence suggested by Jiang and Tian ( 2005 ), that is, Black Scholes implied volatility dominates the forecasting efficiency over the VIX even though both estimates are biased.

JEL Classification: G12, G13, G14, C22
The Minimum Duration of Sensor Data From Which Glycemic Variability Can Be Consistently Assessed
Authors: Neylon Orla M. , Baghurst Peter A. , Cameron Fergus J.
Published: February 2014

Background:

Despite much discussion regarding the clinical relevance of glycemic variation (GV), little discourse has addressed the properties of the data set from which it is derived. We aimed to assess the minimum duration of data required using continuous glucose monitoring (CGM) that most closely approximates to a gold standard 90-day measure.

Methods:

Data from 20 children and adolescents with type 1 diabetes were examined. All participants had CGM data sets of 90 days duration, from which standard deviation (SD), coefficient of variation (CV), mean amplitude of glycemic action (MAGE), and continuous overlapping net glycemic action (CONGA1-8) were calculated for the overall period and then investigational periods of 2, 4, 6, 12, 18, 24, and 30 days. The percentage difference between each measure and the overall measure per time period was assessed.

Results:

As the duration of the CGM data set increased, the percentage error continued to decrease, giving a metric approximating more closely toward the overall measure. Median SD and CV differed from the overall measure by <10% at 12 days duration. The frequency of interruptions to the CGM trace rendered MAGE and CONGA unreliable, hence SD and CV were reported.

Conclusions:

We suggest that data sets used to infer GV should be of a minimum duration of 12 days. MAGE and CONGA exhibit poor performance in the setting of frequent trace interruption.
Uniqueness of positive solutions for several classes of sum operator equations and applications
Authors: Yang Chen , Zhai Chengbo , Hao Mengru
Published: February 2014

In this article we study several classes of sum operator equations on ordered Banach spaces and present some new existence and uniqueness results of positive solutions, which extend the existing corresponding results. Moreover, we establish some pleasant properties of nonlinear eigenvalue problems for several classes of sum operator equations. As applications, we utilize the main results obtained in this paper to study two classes nonlinear problems; one is the integral equationu(t)=λ∫abG(t,s)f(s,u(s))ds, wherefandGare both nonnegative,λ>0is a parameter; the other is the elliptic boundary value problem for the Lane-Emden-Fowler equation−Δu=λf(x,u),u(x)>0in Ω,u(x)=0on∂Ω, where Ω is a bounded domain with smooth boundary inRN(N≥1),λ>0andf(x,u)is allowed to be singular on∂Ω. The new results on the existence and uniqueness of positive solutions for these problems are given, which complement the existing results of positive solutions for these problems in the literature.

MSC:47H10, 47H07, 45G15, 35J60, 35J65.
Global small RNA analysis in fast-growing Arabidopsis thaliana with elevated concentrations of ATP and sugars
Authors: Liang Chao , Liu Xuan , Sun Yuzhe , Yiu Siu-Ming , Lim Boon Leong
Published: February 2014

Background

In higher eukaryotes, small RNAs play a role in regulating gene expression. Overexpression (OE) lines of Arabidopsis thaliana purple acid phosphatase 2 (AtPAP2) were shown to grow faster and exhibit higher ATP and sugar contents. Leaf microarray studies showed that many genes involved in microRNAs (miRNAs) and trans-acting siRNAs (tasiRNAs) biogenesis were significantly changed in the fast-growing lines. In this study, the sRNA profiles of the leaf and the root of 20-day-old plants were sequenced and the impacts of high energy status on sRNA expression were analyzed.

Results

9-13 million reads from each library were mapped to genome. miRNAs, tasiRNAs and natural antisense transcripts-generated small interfering RNAs (natsiRNAs) were identified and compared between libraries. In the leaf of OE lines, 15 known miRNAs increased in abundance and 9 miRNAs decreased in abundance, whereas in the root of OE lines, 2 known miRNAs increased in abundance and 9 miRNAs decreased in abundance. miRNAs with increased abundance in the leaf and root samples of both OE lines (miR158b and miR172a/b) were predicted to target mRNAs coding for Dof zinc finger protein and Apetala 2 (AP2) proteins, respectively. Furthermore, a significant change in the miR173-tasiRNAs-PPR/TPR network was observed in the leaves of both OE lines.

Conclusion

In this study, the impact of high energy content on the sRNA profiles of Arabidopsis is reported. While the abundance of many stress-induced miRNAs is unaltered, the abundance of some miRNAs related to plant growth and development (miR172 and miR319) is elevated in the fast-growing lines. An induction of miR173-tasiRNAs-PPR/TPR network was also observed in the OE lines. In contrast, only few cis- and trans-natsiRNAs are altered in the fast-growing lines.
Does Low-intensity pulsed ultrasound treatment repair articular cartilage injury? A rabbit model study
Authors: Yang Shan-Wei , Kuo Chien-Lin , Chang Shwu Jen , Chen Po-Chou , Lin Yen Ting , Manousakas Ioannis , Kuo Shyh Ming
Published: February 2014

Background

Low-intensity pulsed ultrasound (LIPUS) regiment has been used to treat fractures with non-union and to promote bone union in general. The effect of LIPUS on articular cartilage metabolism has been characterized. Yet, the effect of LIPUS to repair articular cartilage injury remains unclear in vivo.

Methods

We designed a study to investigate the effect of LIPUS on articular cartilage repairing in a rabbit severe cartilage injury model. Eighteen rabbits were divided into three groups: Sham-operated group, operated group without-LIPUS-treatment, operated group with-LIPUS-treatment (a daily 20-minute treatment for 3 months). Full-thickness cartilage defects were surgically created on the right side distal femoral condyle without intending to penetrate into the subchondral bone, which mimicked severe chondral injury. MR images for experimental joints, morphology grading scale, and histopathological Mankin score were evaluated.

Results

The preliminary results showed that the operated groups with-LIPUS-treatment and without-LIPUS-treatment had significantly higher Mankin score and morphological grading scale compared with the sham-operated group. However, there was no significant difference between the with-LIPUS-treatment and without-LIPUS-treatment groups. Cartilage defects filled with proliferative tissue were observed in the with-LIPUS-treatment group grossly and under MR images, however which presented less up-take under Alcian blue stain. Furthermore, no new deposition of type II collagen or proliferation of chondrocyte was observed over the cartilage defect after LIPUS treatment.

Conclusion

LIPUS has no significant therapeutic potential in treating severe articular cartilage injury in our animal study.
Selection of peptides binding to metallic borides by screening M13 phage display libraries
Authors: Ploss Martin , Facey Sandra J , Bruhn Carina , Zemel Limor , Hofmann Kathrin , Stark Robert W , Albert Barbara , Hauer Bernhard
Published: February 2014

Background

Metal borides are a class of inorganic solids that is much less known and investigated than for example metal oxides or intermetallics. At the same time it is a highly versatile and interesting class of compounds in terms of physical and chemical properties, like semiconductivity, ferromagnetism, or catalytic activity. This makes these substances attractive for the generation of new materials. Very little is known about the interaction between organic materials and borides. To generate nanostructured and composite materials which consist of metal borides and organic modifiers it is necessary to develop new synthetic strategies. Phage peptide display libraries are commonly used to select peptides that bind specifically to metals, metal oxides, and semiconductors. Further, these binding peptides can serve as templates to control the nucleation and growth of inorganic nanoparticles. Additionally, the combination of two different binding motifs into a single bifunctional phage could be useful for the generation of new composite materials.

Results

In this study, we have identified a unique set of sequences that bind to amorphous and crystalline nickel boride (Ni3B) nanoparticles, from a random peptide library using the phage display technique. Using this technique, strong binders were identified that are selective for nickel boride. Sequence analysis of the peptides revealed that the sequences exhibit similar, yet subtle different patterns of amino acid usage. Although a predominant binding motif was not observed, certain charged amino acids emerged as essential in specific binding to both substrates. The 7-mer peptide sequence LGFREKE, isolated on amorphous Ni3B emerged as the best binder for both substrates. Fluorescence microscopy and atomic force microscopy confirmed the specific binding affinity of LGFREKE expressing phage to amorphous and crystalline Ni3B nanoparticles.

Conclusions

This study is, to our knowledge, the first to identify peptides that bind specifically to amorphous and to crystalline Ni3B nanoparticles. We think that the identified strong binding sequences described here could potentially serve for the utilisation of M13 phage as a viable alternative to other methods to create tailor-made boride composite materials or new catalytic surfaces by a biologically driven nano-assembly synthesis and structuring.
How mindfulness changed my sleep: focus groups with chronic insomnia patients
Authors: Hubbling Amber , Reilly-Spong Maryanne , Kreitzer Mary Jo , Gross Cynthia R
Published: February 2014

Background

Chronic insomnia is a major public health problem affecting approximately 10% of adults. Use of meditation and yoga to develop mindful awareness (‘mindfulness training’) may be an effective approach to treat chronic insomnia, with sleep outcomes comparable to nightly use of prescription sedatives, but more durable and with minimal or no side effects. The purpose of this study was to understand mindfulness training as experienced by patients with chronic insomnia, and suggest procedures that may be useful in optimizing sleep benefits.

Methods

Adults (N = 18) who completed an 8-week mindfulness-based stress reduction (MBSR) program as part of a randomized, controlled clinical trial to evaluate MBSR as a treatment for chronic insomnia were invited to participate in post-trial focus groups. Two groups were held. Participants (n = 9) described how their sleep routine, thoughts and emotions were affected by MBSR and about utility (or not) of various mindfulness techniques. Groups were audio-recorded, transcribed and analyzed using content analysis.

Results

Four themes were identified: the impact of mindfulness on sleep and motivation to adopt a healthy sleep lifestyle; benefits of mindfulness on aspects of life beyond sleep; challenges and successes in adopting mindfulness-based practices; and the importance of group sharing and support. Participants said they were not sleeping more, but sleeping better, waking more refreshed, feeling less distressed about insomnia, and better able to cope when it occurred. Some participants experienced the course as a call to action, and for them, practicing meditation and following sleep hygiene guidelines became priorities. Motivation to sustain behavioral changes was reinforced by feeling physically better and more emotionally stable, and seeing others in the MBSR class improve. The body scan was identified as an effective tool to enable falling asleep faster. Participants described needing to continue practicing mindfulness to maintain benefits.

Conclusions

First-person accounts are consistent with published trial results of positive impacts of MBSR on sleep measured by sleep diary, actigraphy, and self-report sleep scales. Findings indicate that mindfulness training in a group format, combined with sleep hygiene education, is important for effective application of MBSR as a treatment for chronic insomnia.
Photocurrent response and semiconductor characteristics of Ce-Ce2O3-CeO2-modified TiO2 nanotube arrays
Authors: Tan Yu , Zhang Shenghan , Liang Kexin
Published: February 2014

We reported Ce and its oxide-modified TiO2 nanotube arrays (TNTs) and their semiconductor properties. The TNTs were prepared by anodic oxidation on pure Ti and investigated by electrochemical photocurrent response analysis. Then, the TNT electrodes were deposited of Ce by cathodic reduction of Ce(NO3)3 6H2O. After deposition, the TNT electrodes were fabricated by anodic oxidation at E = 1.0 V(SCE) for various electricity as Ce-Ce2O3-CeO2 modification. The Ce-deposited TNTs (band gap energy E
g = 2.92 eV) exhibited enhanced photocurrent responses under visible light region and indicated more negative flat band potential (E
fb) compared with the TNTs without deposition. After anodic oxidation, the mixed Ce and its oxide (Ce2O3-CeO2)-modified TNT photoelectrodes exhibited higher photocurrent responses under both visible and UV light regions than the TNTs without deposition. The photocurrent responses and E
fb were found to be strongly dependent on the contents of Ce2O3 and CeO2 deposited on TNTs. A new characteristic of E
g = 2.1 ± 0.1 eV was investigated in the Ce2O3- and CeO2-modified photoelectrodes. X-ray diffraction (XRD), scanning electron microscopy (SEM), and X-ray photoelectron spectroscopy (XPS) were also employed to characterize various modified TNTs photoelectrodes.
Protein signatures of oxidative stress response in a patient specific cell line model for autism
Authors: Chiocchetti Andreas G , Haslinger Denise , Boesch Maximilian , Karl Thomas , Wiemann Stefan , Freitag Christine M , Poustka Fritz , Scheibe Burghardt , Bauer Johann W , Hintner Helmut , Breitenbach Michael , Kellermann Josef , Lottspeich Friedrich , Klauck Sabine M , Breitenbach-Koller Lore
Published: February 2014

Background

Known genetic variants can account for 10% to 20% of all cases with autism spectrum disorders (ASD). Overlapping cellular pathomechanisms common to neurons of the central nervous system (CNS) and in tissues of peripheral organs, such as immune dysregulation, oxidative stress and dysfunctions in mitochondrial and protein synthesis metabolism, were suggested to support the wide spectrum of ASD on unifying disease phenotype. Here, we studied in patient-derived lymphoblastoid cell lines (LCLs) how an ASD-specific mutation in ribosomal protein RPL10 (RPL10[H213Q]) generates a distinct protein signature. We compared the RPL10[H213Q] expression pattern to expression patterns derived from unrelated ASD patients without RPL10[H213Q] mutation. In addition, a yeast rpl10 deficiency model served in a proof-of-principle study to test for alterations in protein patterns in response to oxidative stress.

Methods

Protein extracts of LCLs from patients, relatives and controls, as well as diploid yeast cells hemizygous for rpl10, were subjected to two-dimensional gel electrophoresis and differentially regulated spots were identified by mass spectrometry. Subsequently, Gene Ontology database (GO)-term enrichment and network analysis was performed to map the identified proteins into cellular pathways.

Results

The protein signature generated by RPL10[H213Q] is a functionally related subset of the ASD-specific protein signature, sharing redox-sensitive elements in energy-, protein- and redox-metabolism. In yeast, rpl10 deficiency generates a specific protein signature, harboring components of pathways identified in both the RPL10[H213Q] subjects’ and the ASD patients’ set. Importantly, the rpl10 deficiency signature is a subset of the signature resulting from response of wild-type yeast to oxidative stress.

Conclusions

Redox-sensitive protein signatures mapping into cellular pathways with pathophysiology in ASD have been identified in both LCLs carrying the ASD-specific mutation RPL10[H213Q] and LCLs from ASD patients without this mutation. At pathway levels, this redox-sensitive protein signature has also been identified in a yeast rpl10 deficiency and an oxidative stress model. These observations point to a common molecular pathomechanism in ASD, characterized in our study by dysregulation of redox balance. Importantly, this can be triggered by the known ASD-RPL10[H213Q] mutation or by yet unknown mutations of the ASD cohort that act upstream of RPL10 in differential expression of redox-sensitive proteins.
A novel mechanism of regulating breast cancer cell migration via palmitoylation-dependent alterations in the lipid raft affiliation of CD44
Authors: Babina Irina S , McSherry Elaine A , Donatello Simona , Hill Arnold DK , Hopkins Ann M
Published: February 2014

Introduction

Most breast cancer-related deaths result from metastasis, a process involving dynamic regulation of tumour cell adhesion and migration. The adhesion protein CD44, a key regulator of cell migration, is enriched in cholesterol-enriched membrane microdomains termed lipid rafts. We recently reported that raft affiliation of CD44 negatively regulates interactions with its migratory binding partner ezrin. Since raft affiliation is regulated by post-translational modifications including palmitoylation, we sought to establish the contribution of CD44 palmitoylation and lipid raft affiliation to cell migration.

Methods

Recovery of CD44 and its binding partners from raft versus non-raft membrane microdomains was profiled in non-migrating and migrating breast cancer cell lines. Site-directed mutagenesis was used to introduce single or double point mutations into both CD44 palmitoylation sites (Cys286 and Cys295), whereupon the implications for lipid raft recovery, phenotype, ezrin co-precipitation and migratory behaviour was assessed. Finally CD44 palmitoylation status and lipid raft affiliation was assessed in primary cultures from a small panel of breast cancer patients.

Results

CD44 raft affiliation was increased during migration of non-invasive breast cell lines, but decreased during migration of highly-invasive breast cells. The latter was paralleled by increased CD44 recovery in non-raft fractions, and exclusive non-raft recovery of its binding partners. Point mutation of CD44 palmitoylation sites reduced CD44 raft affiliation in invasive MDA-MB-231 cells, increased CD44-ezrin co-precipitation and accordingly enhanced cell migration. Expression of palmitoylation-impaired (raft-excluded) CD44 mutants in non-invasive MCF-10a cells was sufficient to reversibly induce the phenotypic appearance of epithelial-to-mesenchymal transition and to increase cell motility. Interestingly, cell migration was associated with temporal reductions in CD44 palmitoylation in wild-type breast cells. Finally, the relevance of these findings is underscored by the fact that levels of palmitoylated CD44 were lower in primary cultures from invasive ductal carcinomas relative to non-tumour tissue, while CD44 co-localisation with a lipid raft marker was less in invasive ductal carcinoma relative to ductal carcinoma in situ cultures.

Conclusion

Our results support a novel mechanism whereby CD44 palmitoylation and consequent lipid raft affiliation inversely regulate breast cancer cell migration, and may act as a new therapeutic target in breast cancer metastasis.
Utility of thromboelastography and/or thromboelastometry in adults with sepsis: a systematic review
Authors: Müller Marcella C , Meijers Joost CM , Vroom Margreeth B , Juffermans Nicole P
Published: February 2014

Introduction

Coagulation abnormalities are frequent in sepsis. Conventional coagulation assays, however, have several limitations. A surge of interest exists in the use of point-of-care tests to diagnose hypo- and hypercoagulability in sepsis.

We performed a systematic review of available literature to establish the value of rotational thromboelastography (TEG) and thromboelastometry (ROTEM) compared with standard coagulation tests to detect hyper- or hypocoagulability in sepsis patients. Furthermore, we assessed the value of TEG/ROTEM to identify sepsis patients likely to benefit from therapies that interfere with the coagulation system.

Methods

MEDLINE, EMBASE, and the Cochrane Library were searched from 1 January 1980 to 31 December 2012. The search was limited to adults, and language was limited to English. Reference lists of retrieved articles were hand-searched for additional studies. Ongoing trials were searched on http://www.controlled-trials.com and http://www.clinicaltrials.gov. Studies addressing TEG/ROTEM measurements in adult patients with sepsis admitted to the ICU were considered eligible.

Results

Of 680 screened articles, 18 studies were included, of which two were randomized controlled trials, and 16 were observational cohort studies. In patients with sepsis, results show both hyper- and hypocoagulability, as well as TEG/ROTEM values that fell within reference values. Both hyper- and hypocoagulability were to some extent associated with diffuse intravascular coagulation. Compared with conventional coagulation tests, TEG/ROTEM can detect impaired fibrinolysis, which can possibly help to discriminate between sepsis and systemic inflammatory response syndrome (SIRS). A hypocoagulable profile is associated with increased mortality. The value of TEG/ROTEM to identify patients with sepsis who could possibly benefit from therapies interfering with the coagulation system could not be assessed, because studies addressing this topic were limited.

Conclusion

TEG/ROTEM could be a promising tool in diagnosing alterations in coagulation in sepsis. Further research on the value of TEG/ROTEM in these patients is warranted. Given that coagulopathy is a dynamic process, sequential measurements are needed to understand the coagulation patterns in sepsis, as can be detected by TEG/ROTEM.
A multi-split mapping algorithm for circular RNA, splicing, trans-splicing and fusion detection
Authors: Hoffmann Steve , Otto Christian , Doose Gero , Tanzer Andrea , Langenberger David , Christ Sabina , Kunz Manfred , Holdt Lesca M , Teupser Daniel , Hackermüller Jörg , Stadler Peter F
Published: February 2014

Numerous high-throughput sequencing studies have focused on detecting conventionally spliced mRNAs in RNA-seq data. However, non-standard RNAs arising through gene fusion, circularization or trans-splicing are often neglected. We introduce a novel, unbiased algorithm to detect splice junctions from single-end cDNA sequences. In contrast to other methods, our approach accommodates multi-junction structures. Our method compares favorably with competing tools for conventionally spliced mRNAs and, with a gain of up to 40% of recall, systematically outperforms them on reads with multiple splits, trans-splicing and circular products. The algorithm is integrated into our mapping tool (http://www.bioinf.uni-leipzig.de/Software/segemehl/).
Follicular Thyroid Cancers Demonstrate Dual Activation of PKA and mTOR as Modeled by Thyroid-Specific Deletion of Prkar1a and Pten in Mice
Authors: Pringle Daphne R. , Vasko Vasily V. , Yu Lianbo , Manchanda Parmeet K. , Lee Audrey A. , Zhang Xiaoli , Kirschner Jessica M. , Parlow Albert F. , Saji Motoyasu , Jarjoura David , Ringel Matthew D. , La Perle Krista M. D. , Kirschner Lawrence S.
Published: February 2014

Context:

Thyroid cancer is the most common form of endocrine cancer, and it is a disease whose incidence is rapidly rising. Well-differentiated epithelial thyroid cancer can be divided into papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC). Although FTC is less common, patients with this condition have more frequent metastasis and a poorer prognosis than those with PTC.

Objective:

The objective of this study was to characterize the molecular mechanisms contributing to the development and metastasis of FTC.

Design:

We developed and characterized mice carrying thyroid-specific double knockout of the Prkar1a and Pten tumor suppressor genes and compared signaling alterations observed in the mouse FTC to the corresponding human tumors.

Setting:

The study was conducted at an academic research laboratory. Human samples were obtained from academic hospitals.

Patients:

Deidentified, formalin-fixed, paraffin-embedded (FFPE) samples were analyzed from 10 control thyroids, 30 PTC cases, five follicular variant PTC cases, and 10 FTC cases.

Interventions:

There were no interventions.

Main outcome measures:

Mouse and patient samples were analyzed for expression of activated cAMP response element binding protein, AKT, ERK, and mammalian target of rapamycin (mTOR). Murine FTCs were analyzed for differential gene expression to identify genes associated with metastatic progression.

Results:

Double Prkar1a-Pten thyroid knockout mice develop FTC and recapitulate the histology and metastatic phenotype of the human disease. Analysis of signaling pathways in FTC showed that both human and mouse tumors exhibited strong activation of protein kinase A and mTOR. The development of metastatic disease was associated with the overexpression of genes required for cell movement

Conclusions:

These data imply that the protein kinase A and mTOR signaling cascades are important for the development of follicular thyroid carcinogenesis and may suggest new targets for therapeutic intervention. Mouse models paralleling the development of the stages of human FTC should provide important new tools for understanding the mechanisms of FTC development and progression and for evaluating new therapeutics.
Disruption of GIP/GIPR Axis in Human Adipose Tissue Is Linked to Obesity and Insulin Resistance
Authors: Ceperuelo-Mallafré Victòria , Duran Xavier , Pachón Gisela , Roche Kelly , Garrido-Sánchez Lourdes , Vilarrasa Nuria , Tinahones Francisco J. , Vicente Vicente , Pujol Jordi , Vendrell Joan , Fernández-Veledo Sonia
Published: February 2014

Context:

Glucose-dependent insulinotropic peptide (GIP) has a central role in glucose homeostasis through its amplification of insulin secretion; however, its physiological role in adipose tissue is unclear.

Objective:

Our objective was to define the function of GIP in human adipose tissue in relation to obesity and insulin resistance.

Design:

GIP receptor (GIPR) expression was analyzed in human sc adipose tissue (SAT) and visceral adipose (VAT) from lean and obese subjects in 3 independent cohorts. GIPR expression was associated with anthropometric and biochemical variables. GIP responsiveness on insulin sensitivity was analyzed in human adipocyte cell lines in normoxic and hypoxic environments as well as in adipose-derived stem cells obtained from lean and obese patients.

Results:

GIPR expression was downregulated in SAT from obese patients and correlated negatively with body mass index, waist circumference, systolic blood pressure, and glucose and triglyceride levels. Furthermore, homeostasis model assessment of insulin resistance, glucose, and G protein-coupled receptor kinase 2 (GRK2) emerged as variables strongly associated with GIPR expression in SAT. Glucose uptake studies and insulin signaling in human adipocytes revealed GIP as an insulin-sensitizer incretin. Immunoprecipitation experiments suggested that GIP promotes the interaction of GRK2 with GIPR and decreases the association of GRK2 to insulin receptor substrate 1. These effects of GIP observed under normoxia were lost in human fat cells cultured in hypoxia. In support of this, GIP increased insulin sensitivity in human adipose-derived stem cells from lean patients. GIP also induced GIPR expression, which was concomitant with a downregulation of the incretin-degrading enzyme dipeptidyl peptidase 4. None of the physiological effects of GIP were detected in human fat cells obtained from an obese environment with reduced levels of GIPR.

Conclusions:

GIP/GIPR signaling is disrupted in insulin-resistant states, such as obesity, and normalizing this function might represent a potential therapy in the treatment of obesity-associated metabolic disorders.
A Tale of Two Destinies: Georgescu-Roegen on Gossen
Authors: Tubaro Paola
Published: February 2014

Nicholas Georgescu-Roegen edited the English translation of Hermann Heinrich Gossen’s 1854 book The Laws of Human Relations and wrote a lengthy introduction to it. His highly appreciative, thoroughly documented study has become a major reference on an otherwise little-known early writer. It suggests that Gossen was unjustly ignored by his contemporaries, just as Georgescu-Roegen felt that his own contributions to economics were insufficiently recognized. Yet it was not only a personal motive that inspired Georgescu-Roegen’s editorial enterprise: I show that his original plan was to build a model of consumer choice, drawing on Gossen, to address what he saw as essential theoretical issues. The completion of the book project took almost twenty years (it was not published until 1983), during which external circumstances and analytical difficulties gradually eroded the initial theoretical interests, while a sense of self-identification with Gossen gained prominence. As a result, major issues remained ultimately unsolved. The history of economics, originally intended to aid economic theory-building, became the key for sublimating personal feelings into a broader reflection on science in society, beyond time and space differences.
ANGDelMut – a web-based tool for predicting and analyzing functional loss mechanisms of amyotrophic lateral sclerosis-associated angiogenin mutations
Authors: Padhi Aditya K , Vasaikar Suhas V , Jayaram Bhyravabhotla , Gomes James
Published: February 2014

ANGDelMut is a web-based tool for predicting the functional consequences of missense mutations in the angiogenin (ANG) protein, which is associated with amyotrophic lateral sclerosis (ALS). Missense mutations in ANG result in loss of either ribonucleolytic activity or nuclear translocation activity or both of these functions, and in turn cause ALS. However, no web-based tools are available to predict whether a newly identified ANG mutation will possibly lead to ALS. More importantly, no web-implemented method is currently available to predict the mechanisms of loss-of-function(s) of ANG mutants. In light of this observation, we developed the ANGDelMut web-based tool, which predicts whether an ANG mutation is deleterious or benign. The user selects certain attributes from the input panel, which serves as a query to infer whether a mutant will exhibit loss of ribonucleolytic activity or nuclear translocation activity or whether the overall stability will be affected. The output states whether the mutation is deleterious or benign, and if it is deleterious, gives the possible mechanism(s) of loss-of-function. This web-based tool, freely available at http://bioschool.iitd.ernet.in/DelMut/, is the first of its kind to provide a platform for researchers and clinicians, to infer the functional consequences of ANG mutations and correlate their possible association with ALS ahead of experimental findings.
Concepts as hyperintensional objects
Authors: Materna Pavel
Published: February 2014

The author defends the view that the notion of concept, if used in the logical (not cognitivist) tradition, should be explicated procedurally (i.e., not set-theoretically). He argues that Tichý’s Transparent Intensional Logic is an apt tool for such an explication and derives the respective definition. Some consequences of this definition concern the notions of emptiness, simple concepts, empirical concepts and algorithmic concepts.
Logical problems with nonmonotonicity
Authors: Łukowski Piotr
Published: February 2014

A few years ago, believing that human thinking is nonmonotonic, I tried to reconstruct a nonmonotonic reasoning by application of two monotonic procedures. I called them “step forward” and “step backward” (see [4]). The first procedure is just a consequence operation responsible for an extension of the set of beliefs. The second one, defined on the base of the logic of falsehood reconstructed for the given logic of truthfulness, is responsible for a reduction of the set of beliefs. Both procedures taken together were successfully verified by using so-called AGM (see [5]), postulates for expansion, contraction and revision formulated by Alchourrón, Gärdenfors and Makinson (e.g. [1]). Reasoning composed of the mutual application of both procedures seemed to be quite natural for modeling our thinking. At that time, I supposed that it should be nonmonotonic but I was wrong. It turned out impossible to satisfy a definition of the nonmonotonic inference by reasoning composed both steps. To understand why this is impossible, I began to analyze how nonmonotonicity is obtainable in some well-known cases in the literature. I analyzed the problem from two points of view: (1) non-formal examples for nonmonotonicity and (2) formal constructions of nonmonotonic operations/relations. The result of those investigations was astonishing: none of the considered by me cases of nonmonotonicity belonging to point (1) and almost none belonging to (2) satisfies the definition of nonmonotonic inference. Arguments against the nonmonotonic character of well-known examples for nonmonotonicity of human thinking are more precisely presented in [6]. I present them below an abbreviated version of them.
Just the Faces: Exploring the Effects of Facial Features in Print Advertising
Authors: Xiao Li , Ding Min
Published: February 2014

Human faces are used extensively in print advertisements. In prior literature, researchers have studied spokespersons in general, but few have studied faces explicitly. This paper aims to answer three questions that are important to both researchers and practitioners: (1) Do faces affect how a viewer reacts to an advertisement on the metrics that advertisers care about? (2) If faces do have an effect, is it large enough to warrant careful selection of faces when constructing print advertisements? (3) If faces do have an effect and the effect is large, what facial features elicit such differential reactions on these metrics, and are such reactions different across individuals and/or product categories? Relying on the eigenface method, a holistic approach widely used in the computer science field for face recognition, we conducted an empirical study to answer these three questions. The results show that different faces do have an effect on people's attitude toward the advertisement, attitude toward the brand, and purchase intention and that the effect is nontrivial. Multiple segments were identified and substantial differences were found among people's reactions to the faces in the ads across those segments. We also found that the effect of faces interacts with product categories and is mediated by various facial traits such as attractiveness, trustworthiness, and competence. Implications and directions for future research are discussed.
Management Insights
Authors: Gorman Michael F.
Published: February 2014

In our monthly Management Insights we highlight—without using technical jargon—the insights and implications for practicing managers that are explored and developed in each article published in the issue.
Expression and Prognostic Significance of APE1/Ref-1 and NPM1 Proteins in High-Grade Ovarian Serous Cancer
Authors: Londero Ambrogio P. , Orsaria Maria , Tell Gianluca , Marzinotto Stefania , Capodicasa Valentina , Poletto Mattia , Vascotto Carlo , Sacco Cosimo , Mariuzzi Laura
Published: February 2014

Objectives:

To correlate the expression profile of human apurinic endonuclease/redox factor 1 (APE1/Ref-1) with that of nucleolar/nucleoplasmic protein nucleophosmin 1 (NPM1) in association with the aggressiveness and progression of high-grade ovarian serous cancer.

Methods:

Retrospective study analyzing a tissue microarray of 73 women affected by high-grade ovarian serous cancer. Protein expression was assessed by immunohistochemistry on primary tumor masses and synchronous peritoneal metastases if present.

Results:

APE1/Ref-1 and NPM1 showed a significant correlation in ovarian serous cancer. Patients with a poorer outcome showed a significant overexpression of nuclear NPM1 protein. A Cox proportional hazards multivariate regression model revealed NPM1 expression to be independently significant for overall survival in high-grade ovarian serous cancers after correcting for stage, age, cytoreduction completeness, and platinum resistance.

Conclusions:

APE1/Ref-1 interacts with NPM1 to control the DNA damage repair system, and it is likely that this interaction plays a defining role in high-grade ovarian serous carcinoma. A high NPM1 immunohistochemical expression was independently correlated with a shorter survival period and thus appears to be an important prognostic factor.