bluuebunny/crossref_metadata_2025 huggingface dataset:
In vivo and in vitro metabolism of the synthetic cannabinoid JWH‐200
Authors: De Brabanter Nik , Esposito Simone , Tudela Eva , Lootens Leen , Meuleman Philip , Leroux‐Roels Geert , Deventer Koen , Eenoo Peter Van
Published: August 2013

RATIONALE

The synthetic cannabinoid JWH‐200 (1‐[2‐(4‐morpholinyl)ethyl]‐3‐(1‐naphthoyl)‐indole) appeared on the market around 2009. In order to identify markers for misuse of this compound and allow for the development of adequate routine methods, the metabolism of this compound was investigated using two models.

METHODS

In vitro and in vivo (both with and without enzymatic hydrolysis) samples were purified by solid‐phase extraction and analyzed using liquid chromatography. Electrospray ionization high‐resolution Orbitrap mass spectrometry was used for the identification of the metabolites. To confirm the results in vivo, triple‐quadrupole mass spectrometry was employed

RESULTS

In the in vitro model, using human liver microsomes, 22 metabolites were detected which could be divided into 11 metabolite classes. By using the chimeric mouse model with humanized liver, most of these metabolites were confirmed in vivo. It was found that all metabolites are excreted in urine as conjugates, mostly as glucuronides with varying conjugation rates.

CONCLUSIONS

The metabolite formed by consecutive morpholine cleavage and oxidation of the remaining side chain to a carboxylic group was detected in the highest amounts with the longest detection time. Therefore, it is the best candidate metabolite to detect JWH‐200 abuse in urine. Copyright © 2013 John Wiley & Sons, Ltd.
A Square Peg in a Round Hole? Challenges with DALY‐based “Burden of Disease” Calculations in Surgery and a Call for Alternative Metrics
Authors: Gosselin Richard , Ozgediz Doruk , Poenaru Dan
Published: August 2013

Introduction

In recent years, surgical providers and advocates have engaged in a growing effort to establish metrics to estimate capacity for surgical services as well the burden of surgical diseases in resource‐limited settings. The burden of disease (BoD) studies have established the disability‐adjusted life year (DALY) as the primary metric to measure both disability and premature mortality. Nonetheless, DALY‐based approaches present methodological challenges, some of which are unique to surgical conditions, not fully addressed through the multiple iterations of the BoD studies, including the most recent study.

Methods and Results

This paper examines these challenges in detail, including issues around age‐weighting and discounting, and estimates of disability‐weights for specific conditions. Surgical burden measurements of specific conditions, or through the assessment of hospital wards as platforms for service delivery, still have unresolved methodological hurdles. The 2010 BoD study addresses some of these issues, but many questions still remain. Other methods estimating surgical prevalence, backlogs in treatment, and disability incurred by delays in care may provide more practical approaches to disease burden that can be useful tools for clinicians and health advocates.

Conclusions

These approaches warrant further exploration in LMICs and these debates require active engagement by surgical providers and advocates globally.
Treatment of Large Acetabular Defects: A Surgical Technique Utilizing Impaction Grafting into a Metallic Mesh
Authors: Buckup Johannes , Salinas Emiliano Alvarez , Valle Alejandro Gonzalez Della , Boettner Friedrich
Published: August 2013

Background

Revision total hip arthroplasty in cases with severe acetabular bone loss is challenging. In the presence of combined cavitary and segmental defects without superior acetabular coverage, reconstructions with a structural acetabular allograft protected by a cage or a custom-made triflange cage have been the treatment of choice. The current paper describes an impaction grafting into a mesh for uncontained defects in revision total hip arthroplasty.

Description of Technique

After restoring containment with a mesh fixed with small fragment screws, defects were restored using impaction grafting combined with a cemented all-polyethylene cup.

Patients and Methods

Fourteen consecutive acetabular impaction graftings were performed by two surgeons. All patients had a type 3B defect according to the Paprosky classification.

Results

No re-revisions or radiographic failure was detected in the early follow-up period.

Conclusion

Impaction grafting into a mesh is an interesting treatment option to restore bone in combined cavitary and segmental defects.
Characterization of Enzymatically Interesterified Canola Oil and Fully‐Hydrogenated Canola Oil Blends Under Supercritical CO2
Authors: Jenab Ehsan , Temelli Feral
Published: August 2013

Blends of canola oil and fully‐hydrogenated canola oil (FHCO) containing 10, 30, and 50 wt% FHCO were interesterified enzymatically using Lipozyme TL IM (6 % of initial substrates, w/v) under supercritical CO2 at 10 MPa and 65 °C for 2 h. Changes in polymorphic behavior and crystal morphology of non‐interesterified initial blends (NIB) and purified enzymatically interesterified products (PEIP) were studied using X‐ray diffraction spectroscopy (XRD) and polarized light microscopy. As well, the effects of blend ratio and enzymatic interesterification on rheological behavior were investigated. XRD analysis demonstrated the predominance of α form in FHCO while blending it with canola oil induced the formation of β form after crystallizing the samples at 24 and 5 °C for 12 h. Enzymatic interesterification caused the appearance of β′ forms and dramatically changed crystal morphology. The PEIP samples contained fewer crystal particles compared to NIB, but the crystals were more symmetrical. The elastic modulus (solid‐like behavior) (G′) was lower in NIB with 30 wt% FHCO compared to the one with 50 wt% FHCO. Enzymatic interesterification also had a strong effect on G′ of the samples as it decreased after interesterification. The results of this study will help the development of conversion technologies under supercritical conditions in order to formulate more healthy fats having appropriate functional properties to address the industrial demand for the production of margarine and pastry shortenings.
ABA‐insensitive (ABI) 4 and ABI5 synergistically regulate DGAT1 expression in Arabidopsis seedlings under stress
Authors: Kong Yinfei , Chen Songbin , Yang Yang , An Chengcai
Published: August 2013

Triacylglycerol (TAG) accumulation is essential for seed maturation in plants. Diacylglycerol acyltransferase 1 (DGAT1) is the rate‐limiting enzyme in TAG biosynthesis. In this study, we show that TAG accumulation in Arabidopsis seedlings is correlated with environmental stress, and both ABI4 and ABI5 play important roles in regulating DGAT1 expression. Tobacco transient assays revealed the synergistic effect of ABI4 with ABI5 in regulating DGAT1 expression. Taken together, our findings indicate ABI5 is an important accessory factor with ABI4 in the activation of DGAT1 in Arabidopsis seedlings under stress.
Evidence for reciliation of RPE1 cells in late G1 phase, and ciliary localisation of cyclin B1
Authors: Spalluto Cosma , Wilson David I. , Hearn Tom
Published: August 2013

The primary cilium, an organelle that transduces extracellular signals important for development and tissue homeostasis, is typically assembled upon cell cycle exit and disassembled upon cell cycle re‐entry. Cilium assembly is thought to be suppressed in cycling cells, however the extent of suppression is not clear. For example, primary cilia are present in certain proliferating cells during development, and a period of reciliation has been reported to occur in late G1 in murine 3T3 cells released from serum starvation‐induced quiescence. Human retinal pigmented epithelial (hTERT‐RPE1; herein, RPE1) cells are commonly used to investigate pathways regulating cilium disassembly, however the ciliary disassembly profile of these cells remains uncertain. A period of reciliation has not been observed. Here, we analyse the ciliary disassembly profile of RPE1 cells by immunofluorescence microscopy. The results suggest a profile similar to 3T3 cells, including a period of reciliation in late G1 and a second wave of deciliation in S phase. We present evidence that arresting cells in early S phase with hydroxyurea or excess thymidine prevents the second wave of deciliation, and that deciliation is initiated shortly after release from a thymidine block, consistent with coupling to DNA replication. These findings support the often overlooked notion that cilium formation can occur in late G1, and suggest that RPE1 cells could serve as a model system for studying the molecular pathways that direct this process, in addition to those that stimulate cilium disassembly. We also present immunofluorescence data indicating that cyclin B1 localises to primary cilia.
Turbulent transport of a high-Schmidt-number scalar near an air–water interface
Authors: Variano Evan A. , Cowen Edwin A.
Published: August 2013

We measure solute transport near a turbulent air–water interface at which there is zero mean shear. The interface is stirred by high-Reynolds-number homogeneous isotropic turbulence generated far below the surface, and solute transport into the water is driven by an imposed concentration gradient. The air–water interface is held at a constant concentration much higher than that in the bulk of the water by maintaining pure${\mathrm{CO} }_{2} $gas above a water tank that has been initially purged of dissolved${\mathrm{CO} }_{2} $. We measure velocity and concentration fluctuations below the air–water interface, from the viscous sublayer to the middle of the ‘source region’ where the effects of the surface are first felt. Our laboratory measurement technique uses quantitative imaging to collect simultaneous concentration and velocity fields, which are measured at a resolution that reveals the dynamics in the turbulent inertial subrange. Two-point statistics reveal the spatial structure of velocity and concentration fluctuations, and are examined as a function of depth beneath the air–water interface. There is a clear dominance of large scales at all depths for all quantities, but the relative importance of scales changes markedly with proximity to the interface. Quadrant analysis of the turbulent scalar flux shows a four-way balance of flux components far from the interface, which near the interface evolves into a two-way balance between motions that are raising and lowering parcels of low-concentration fluid.
Turbulent spots in a channel: large-scale flow and self-sustainability
Authors: Lemoult Grégoire , Aider Jean-Luc , Wesfreid José Eduardo
Published: August 2013

Using a large-time-resolved particle image velocimetry field of view, a developing turbulent spot is followed in space and time in a rectangular channel flow for more than 100 advective time units. We show that the flow can be decomposed into a large-scale motion consisting of an asymmetric quadrupole centred on the spot and a small-scale part consisting of streamwise streaks. From the temporal evolution of the energy of the streamwise and spanwise velocity perturbations, it is suggested that a self-sustaining process can occur in a turbulent spot above a given Reynolds number.
Screening and assessment instruments for use in Indigenous-specific alcohol and drug treatment rehabilitation
Authors: Stephens Anne , Bohanna India , Graham Deborah , Clough Alan R.
Published: August 2013

Objective: The study's aim was to review instruments suitable for assessing Australian Indigenous clients’ treatment needs, and changes in wellbeing while receiving treatment for substance misuse at a culturally competent residential setting in north Queensland, Australia.

Method: Searches of electronic databases, previously published reviews and websites was conducted. Instruments were selected according to their use in alcohol and drug treatment, developed for and/or validated with Australian Indigenous populations and applicability to measuring wellbeing.

Findings: Forty instruments were identified and their characteristics summarised according to five descriptive categories: (1) evidence of psychometric utility and previous use in alcohol and drug treatment settings, (2) developed for, used with, and/or validated specifically for Australian Indigenous populations, (3) a flexible administrative method of self-report and/or interview, (4) an administration time of less than 20 minutes and (5) freely accessible in the public domain.

Conclusions: Few instruments were found to have been validated specifically for use with Australian Indigenous people for use in drug and alcohol treatment. In order to measure wellbeing change and effective treatment, it may be possible to appropriately modify mainstream instruments, however, validation and sensitivity assessment of instruments for use with Australian Aboriginal and Torres Strait Islander people, is urgently required.
Digital History Anthologies on the Web:German History in Documents and Images
Authors: McCullough Kelly , Retallack James
Published: August 2013

Initial public offerings (IPOs) in the dot-com world do not always turn out to be the darlings they are expected to be. Ask Mark Zuckerberg about Facebook's IPO in May 2012. But even successful new ventures often defy their founders' expectations. As we hope to suggest in the following report,German History in Documents and Images(GHDI)—a project that has put thousands of primary source texts, drawings, photographs, and maps on the internet, along with hundreds of pages of accompanying commentary—has drawn critical appreciation from specialists and nonspecialists alike, but it has also raised thorny questions about authorship, authority, and audience. Those questions concern the writing of history in general and the newer, more specific discipline of “history on the web.” Like the project itself, this report is the result of a collaboration among the GHDI project staff, which is based at the German Historical Institute (GHI), Washington, D.C., and the GHDI volume editors, all of whom teach (or taught) German history at colleges and universities in North America. In the following pages, we will discuss the origins and early goals of the project, describe the challenges associated with the realization of a large, collaborative history project of this nature—whether in book or digital form—and reflect upon what we perceive as the promise and perils of digital history anthologies.
The Land and Labour League
Authors: Weston John , Boons Martin J. , George Eccarius J.
Published: August 2013

“Whereas the existence and rapid increase of poverty and pauperism amongst the industrial classes, side by side with the equally rapid increase and development of the scientific appliances of production, is an anomaly that demonstrates the existence of radical and fundamental defects in the arrangements of society, which it is the incumbent and imperative duty of all classes of Reformers to use their utmost endeayours to discover and remove, this Conference recommends thate a vigorous, outspoken, and manly exposition of the causes of this anomalous state of things, with a view to its eradication, be forthwith set on foot by an Association to be now formed under the title of the ‘Political and Social Reform League’.”
Designing and developing a literature-derived, population-based dietary inflammatory index
Authors: Shivappa Nitin , Steck Susan E , Hurley Thomas G , Hussey James R , Hébert James R
Published: August 2013

Objective

To design and develop a literature-derived, population-based dietary inflammatory index (DII) to compare diverse populations on the inflammatory potential of their diets.

Design

Peer-reviewed primary research articles published through December 2010 on the effect of diet on inflammation were screened for possible inclusion in the DII scoring algorithm. Qualifying articles were scored according to whether each dietary parameter increased (+1), decreased (−1) or had no (0) effect on six inflammatory biomarkers: IL-1β, IL-4, IL-6, IL-10, TNF-α and C-reactive protein.

Setting

The Dietary Inflammatory Index Development Study was conducted in the Cancer Prevention and Control Program of the University of South Carolina in Columbia, SC, USA from 2011 to 2012.

Results

A total of ≈6500 articles published through December 2010 on the effect of dietary parameters on the six inflammatory markers were screened for inclusion in the DII scoring algorithm. Eleven food consumption data sets from countries around the world were identified that allowed individuals’ intakes to be expressed relative to the range of intakes of the forty-five food parameters observed across these diverse populations. Qualifying articles (n 1943) were read and scored based on the forty-five pro- and anti-inflammatory food parameters identified in the search. When fit to this composite global database, the DII score of the maximally pro-inflammatory diet was +7·98, the maximally anti-inflammatory DII score was −8·87 and the median was +0·23.

Conclusions

The DII reflects both a robust literature base and standardization of individual intakes to global referent values. The success of this first-of-a-kind attempt at relating intakes of inflammation-modulating foods relative to global norms sets the stage for use of the DII in a wide variety of epidemiological and clinical studies.
Mediterranean diet adherence rates in Sicily, southern Italy
Authors: Grosso Giuseppe , Marventano Stefano , Giorgianni Gabriele , Raciti Teodoro , Galvano Fabio , Mistretta Antonio
Published: August 2013

Objective

To assess adherence to the Mediterranean diet and nutrient intakes in a population of Sicily, southern Italy and to evaluate possible determinants, particularly socio-cultural and lifestyle factors.

Design

Cross-sectional.

Setting

Urban and rural areas of eastern Sicily.

Subjects

Between May 2009 and December 2010, 3090 adults were randomly recruited through the collaboration of fourteen general practitioners. Adherence to the Mediterranean diet was measured by the MedDietScore. Nutrient intakes were assessed through the 24 h recall of the previous day's dietary intake.

Results

Rural participants were barely more adherent to the Mediterranean diet than their urban counterparts (mean scores were 27·8 and 27·2, respectively, P = 0·037). The MedDietScore was correlated with intakes of MUFA, fibre and vitamin C, as well as with consumption of non-refined cereals, vegetables, fruit, meat, dairy products, alcohol and nuts. Regression analysis revealed that older and more educated people were more likely to be in the highest tertile of MedDietScore (OR = 1.90; 95 % CI 1·39, 2·59 and OR = 1·29; 95 % CI 1·05, 1·58, respectively). A significant difference in quantity (moderate) and quality (red wine and beer) of alcohol was found according to adherence to the Mediterranean diet. Finally, more active participants were 1·5 times more likely to form part of the high-adherence group.

Conclusions

A slow but concrete moving away from traditional patterns has been observed in younger people and low educated people. Public health interventions should focus on these target populations in order to improve the quality of their diet.
Nondestructive Characterization and Enzyme Cleaning of Painted Surfaces: Assessment from the Macro to Nano Level
Authors: Pereira Catarina , Busani Tito , Branco Luis C. , Joosten Ineke , Sandu Irina Crina Anca
Published: August 2013

This work establishes a multiscale and multitechnique nondestructive approach as valid methodology for monitoring surface properties and evaluating the effectiveness of enzymatic removal of varnishes from paintings/polychrome artefacts.

Mock-up samples (documented reconstructions of oil, tempera, and gilded layers on canvas and wooden supports) were covered with different proteinaceous varnishes (egg white, animal and fish glue, casein) and then characterized before and after the removal of these coatings with enzyme-based solutions. The varnish was cleaned in several steps (two dry swabs and two wet swabs) with a clearance step for removing the residues from proteinaceous varnish or from enzyme solution.

Microscopy [stereomicroscopy (SM), optical microscopy (OM), atomic force microscopy (AFM), and scanning electron microscopy (SEM)] and colorimetric (CIEL*a*b* system) techniques were used for characterization of the reconstruction surfaces at different scales (macro-scale by SM and OM; micro-scale by SEM and nano-scale by AFM). These techniques were also used to monitor the cleaning treatment.

Although results presented in this work were obtained for the specific treatment of enzyme removal, the methodology could be extended to other types of materials and cleaning. Further experiments on real works of art are needed for a complete validation of the methodology.
Inversions afterundas a V1 Pattern in Middle High German: Information- and Discourse-Structural Aspects
Authors: Coniglio Marco , Schlachter Eva
Published: August 2013

In the following paper, we claim that the so-calledInversionen nach undare instances of V1 clauses. Although these constructions are attested from Old High German to the 19th century, we focus on the Middle High German period. Our arguments are based upon information- and discourse-structural properties. These clauses share typical properties of V1 clauses, namely, the absence of a topic-comment division, their relevance for textual cohesion, the accessibility status of the subject, the lexical semantics of their predicate, and their expressivity.*
The Imperative ofSayas a Pragmatic Marker in English and Dutch
Authors: Van Olmen Daniël
Published: August 2013

This article examines the imperative ofsayas a pragmatic marker in English and Dutch. Present-daysayandzeg‘say’ are contrasted on the basis of comparable corpus data. This comparison, together with additional diachronic data, serves as input for a study of the typical developments of the imperative ofsayas a pragmatic marker. Further-more, on the basis of a wider range of European and other languages, the article explores the possibility of the developments in English and Dutch being an areal phenomenon.*
The relationship between body image, age, and distress in women facing breast cancer surgery
Authors: Miller Sarah J. , Schnur Julie B. , Weinberger-Litman Sarah L. , Montgomery Guy H.
Published: August 2013

Objectives:

Research suggests that the strength of the relationship between body image and emotional distress decreases with age. Past research has focused on expected aging-related body changes, and has not yet examined unexpected body changes (e.g., breast cancer surgery). The present post-hoc study assessed relationships between age, body image, and emotional distress in women facing breast cancer surgery.

Methods:

Older (≥65 years, n = 40) and younger (<65 years, n = 40) women were matched on race/ethnicity, marital status, and surgery type. Within one week prior to surgery, participants completed measures of demographics, aspects of body image, and emotional distress (general and surgery-specific).

Results:

Results indicated that: (1) body image did not differ by age (p > 0.999); (2) older women reported less pre-surgical emotional distress than younger women (p's < 0.01); and, (3) age moderated the relationship between body image and emotional distress (p's < 0.06).

Significance of results:

The results suggest that younger women, particularly those with poor body image, are at an increased risk for pre-surgical emotional distress. These women may benefit from pre-surgical interventions designed to improve body image or to reduce pre-surgical emotional distress.
Genetic diversity analysis of a potato (Solanum tuberosumL.) collection including Chiloé Island landraces and a large panel of worldwide cultivars
Authors: Esnault F. , Solano J. , Perretant M. R. , Hervé M. , Label A. , Pellé R. , Dantec J. P. , Boutet G. , Brabant P. , Chauvin J. E.
Published: August 2013

In order to investigate further the interest of using the Chilean gene pool in potato breeding programmes, the genetic diversity and population structure of a collection ofSolanum tuberosumL. genotypes including 350 worldwide varieties or breeders' lines (referred to as the modern group) and 30 Chiloé Island landraces were examined using simple sequence repeat markers. The close genetic proximity of the Chiloé Island landraces to the modern group was confirmed using several structure analysis methods: principal coordinate analysis; hierarchical clustering analysis; analysis of molecular variance; Bayesian model-based clustering analysis. The latter analysis, in particular, revealed no clear genetic structure between the modern group and the Chiloé Island landraces. The Chiloé Island germplasm appears to represent an interesting gene pool that could be exploited in potato breeding programmes using an association mapping approach.
LRRFIP2 negatively regulates NLRP3 inflammasome activation in macrophages by promoting Flightless-I-mediated caspase-1 inhibition
Authors: Jin Jing , Yu Qian , Han Chaofeng , Hu Xiang , Xu Sheng , Wang Qingqing , Wang Jianli , Li Nan , Cao Xuetao
Published: August 2013

The NLRP3 inflammasome is the most characterized inflammasome activated by cellular infection or stress, which is responsible for the maturation of proinflammatory cytokines IL-1β and IL-18. The precise molecular mechanism for negative regulation of NLRP3 inflammasome activation needs to be further defined. Here we identify leucine-rich repeat Fli-I-interacting protein 2 (LRRFIP2) as an NLRP3-associated protein and an inhibitor for NLRP3 inflammasome activation. LRRFIP2 binds to NLRP3 via its N terminus upon NLRP3 inflammasome activation, and also interacts with Flightless-I, a pseudosubstrate of caspase-1, via its Coil motif. Knockdown of Flightless-I significantly promotes NLRP3 inflammasome activation. LRRFIP2 enhances the interaction between Flightless-I and caspase-1, facilitating the inhibitory effect of Flightless-I on caspase-1 activation. Furthermore, silencing of Flightless-I abrogates the inhibitory effect of LRRFIP2 on NLRP3 inflammasome. These data demonstrate that LRRFIP2 inhibits NLRP3 inflammasome activation by recruiting the caspase-1 inhibitor Flightless-I, thus outlining a new mechanism for negative regulation of NLRP3 inflammasome.
Assessment of Maraviroc Exposure–Response Relationship at 48 Weeks in Treatment‐Experienced HIV‐1–Infected Patients in the MOTIVATE Studies
Authors: Jacqmin P , Wade JR , Weatherley B , Snoeck E , Marshall S , McFadyen L
Published: August 2013

Efficacy exposure–response relationships of the CCR5 antagonist maraviroc were evaluated across two phase III clinical trials. This post‐hoc analysis used 48‐week efficacy data from 841 treatment‐experienced patients infected with CCR5‐tropic human immunodeficiency virus type 1 (HIV‐1), identified by the enhanced sensitivity Trofile assay. Probability of treatment success (viral RNA <50 copies/ml) was modeled using generalized additive logistic regression, testing exposure, clinical, and virologic variables. Prognostic factors for treatment success (in decreasing order of Akaike information criterion (AIC) change) were: maraviroc treatment, high‐weighted overall susceptibility to background treatment, absence of an undetectable maraviroc concentration, high baseline CD4 count (BCD4), low viral load (VL), race (other than black), absence of non‐R5 baseline tropism (BTRP), and absence of fosamprenavir (FPV). No concentration–response relationship was found with treatment (maraviroc vs. placebo) and presence/absence of undetectable maraviroc concentration (adherence marker) in the model. The maraviroc doses studied (300 or 150 mg with potent CYP3A4 inhibitors once (q.d.)/twice daily (b.i.d.)) deliver concentrations near the top of the concentration–response curve.

CPT: Pharmacometrics & Systems Pharmacology (2013) 2, e64; doi:10.1038/psp.2013.42; published online 14 August 2013
Identification of protein phosphatase 1 as a regulator of the LRRK2 phosphorylation cycle
Authors: Lobbestael Evy , Zhao Jing , Rudenko Iakov N. , Beylina Aleksandra , Gao Fangye , Wetter Justin , Beullens Monique , Bollen Mathieu , Cookson Mark R. , Baekelandt Veerle , Nichols R. Jeremy , Taymans Jean-Marc
Published: August 2013

A cluster of phosphorylation sites in LRRK2 (leucine-rich repeat kinase 2), including Ser910, Ser935, Ser955 and Ser973, is important for PD (Parkinson's disease) pathogenesis as several PD-linked LRRK2 mutants are dephosphorylated at these sites. LRRK2 is also dephosphorylated in cells after pharmacological inhibition of its kinase activity, which is currently proposed as a strategy for disease-modifying PD therapy. Despite this importance of LRRK2 dephosphorylation in mutant LRRK2 pathological mechanism(s) and in LRRK2′s response to inhibition, the mechanism by which this occurs is unknown. Therefore we aimed to identify the phosphatase for LRRK2. Using a panel of recombinant phosphatases, we found that PP1 (protein phosphatase 1) efficiently dephosphorylates LRRK2 in vitro. PP1 activity on LRRK2 dephosphorylation was confirmed in cells using PP1 inhibition to reverse LRRK2 dephosphorylation induced by the potent LRRK2 kinase inhibitor LRRK2-IN1 as well as in R1441G mutant LRRK2. We also found that PP1 and LRRK2 can form a complex in cells. Furthermore, we observed that PP1 inhibition modulates LRRK2′s cellular phenotype by reducing skein-like LRRK2-positive structures associated with dephosphorylation. In conclusion, the present study reveals PP1 as the physiological LRRK2 phosphatase, responsible for LRRK2 dephosphorylation observed in PD mutant LRRK2 and after LRRK2 kinase inhibition.
New analytical approach to detection threshold of a dynamic programming track‐before‐detect algorithm
Authors: Liu Shulin , Chen Xinliang , Zeng Tao , Zheng Le
Published: August 2013

Maintaining the constant false alarm rate (CFAR) is an important issue for the dynamic programming‐based track‐before‐detect (DP‐TBD) in low signal‐to‐noise ratio environment. However, the existing method for analysing the false alarm probability, based on extreme value theory (EVT), leads to the inaccuracy of the obtained detection threshold. In this study, a new analytical approach to compute the false alarm probability of DP‐TBD is presented. In the proposed method, the generalised Pareto distribution is utilised to approximate the false alarm probability based on the peaks over threshold model, which can maintain CFAR for DP‐TBD method in the low signal‐to‐noise environment effectively. Simulation results show that this approach provides a more accurate false alarm probability estimation than previous EVT methods.
Studies on the Enantioselective Synthesis of Carbazolones as Intermediates in Aspidosperma and Kopsia Alkaloid Synthesis
Authors: Gartshore Christopher J. , Lupton David W.
Published: August 2013

Two strategies for the assembly of homochiral carbazolones have been investigated. The first exploited desymmetrisation of 1,3-cyclohexadione derivatives however this failed to deliver satisfactory outcomes. An orthogonal route exploiting palladium catalysed decarboxylative allylation of racemic carbazolone β-ketoesters has been developed. Herein we report full details on the development of this reaction and clarify apparent discrepancies between our preliminary reports and those of Shao.
Was heißt es: Einen philosophischen Text historisch lesen?
Authors: Flasch Kurt
Published: August 2013

Abstract
In his later thought, Martin Heidegger disclaimed the possibility of a philosophical history of philosophy. In his view, the history of philosophy tends to remain bound to a specißc philosophical orientation and offer merely a philosophical position, not philosophy itself, presenting at best nothing more than an assemblage of doctrinal positions. In contrast, Heidegger developed in his early Freiburg lectures of 1919-1923 an historical-phenomenological program of philosophical history directed against the historical school of Dilthey, whose objekthi-storisch perspective he meant to replace with his own vollzugshistorisch method. For Heidegger, there is no perfected subject at the basis of historical investigation, but rather it is the temporality of the observer which makes possible historical knowledge in the ßrst place. Heidegger's later abandonment of this notion is a significant reason for the lack of a philosophical approach to writing the history of philosophy after 1945 in Germany.
Blocks with central product defect group 𝐷_{2ⁿ}∗𝐶_{2^{𝑚}}
Authors: Sambale Benjamin
Published: August 2013

We determine the numerical invariants of blocks with defect group

D

2
n

∗

C

2
m

≅

Q

2
n

∗

C

2
m

D_{2^n}\ast C_{2^m}\cong Q_{2^n}\ast C_{2^m}

(central product), where

n
≥
3

n\ge 3

and

m
≥
2

m\ge 2

. As a consequence, we prove Brauer’s

k
(
B
)

k(B)

-conjecture, Olsson’s conjecture (and more generally Eaton’s conjecture), Brauer’s height zero conjecture, the Alperin-McKay conjecture, Alperin’s weight conjecture and Robinson’s ordinary weight conjecture for these blocks. Moreover, we show that the gluing problem has a unique solution in this case. This paper continues B. Sambale, Blocks with defect group

D

2
n

×

C

2
m

D_{2^n}\times C_{2^m}

, J. Pure Appl. Algebra 216 (2012), 119–125.
Joint haplotype phasing and genotype calling of multiple individuals using haplotype informative reads
Authors: Zhang Kui , Zhi Degui
Published: August 2013

Motivation: Hidden Markov model, based on Li and Stephens model that takes into account chromosome sharing of multiple individuals, results in mainstream haplotype phasing algorithms for genotyping arrays and next-generation sequencing (NGS) data. However, existing methods based on this model assume that the allele count data are independently observed at individual sites and do not consider haplotype informative reads, i.e. reads that cover multiple heterozygous sites, which carry useful haplotype information. In our previous work, we developed a new hidden Markov model to incorporate a two-site joint emission term that captures the haplotype information across two adjacent sites. Although our model improves the accuracy of genotype calling and haplotype phasing, haplotype information in reads covering non-adjacent sites and/or more than two adjacent sites is not used because of the severe computational burden.

Results: We develop a new probabilistic model for genotype calling and haplotype phasing from NGS data that incorporates haplotype information of multiple adjacent and/or non-adjacent sites covered by a read over an arbitrary distance. We develop a new hybrid Markov Chain Monte Carlo algorithm that combines the Gibbs sampling algorithm of HapSeq and Metropolis–Hastings algorithm and is computationally feasible. We show by simulation and real data from the 1000 Genomes Project that our model offers superior performance for haplotype phasing and genotype calling for population NGS data over existing methods.

Availability: HapSeq2 is available at www.ssg.uab.edu/hapseq/.

Contact:  dzhi@uab.edu or kzhang@uab.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
TFcheckpoint: a curated compendium of specific DNA-binding RNA polymerase II transcription factors
Authors: Chawla Konika , Tripathi Sushil , Thommesen Liv , Lægreid Astrid , Kuiper Martin
Published: August 2013

Summary: Gene regulatory network assembly and analysis requires high-quality knowledge sources that cover functional aspects of the various components of the gene regulatory machinery. A multiplicity of resources exists with information about mammalian transcription factors (TFs); yet, only few of these provide sufficiently accurate classifications of the functional roles of individual TFs, or standardized evidence that would justify the information on which these functional classifications are based. We compiled the list of all putative TFs from nine different resources, ignored factors such as general TFs, mediator complexes and chromatin modifiers, and for the remaining factors checked the available literature for references that support their function as a true sequence-specific DNA-binding RNA polymerase II TF (DbTF). The results are available in the TFcheckpoint database, an exhaustive collection of TFs annotated according to experimental and other evidence on their function as true DbTFs. TFcheckpoint.org provides a high-quality and comprehensive knowledge source for genome-scale regulatory network studies.

Availability: The TFcheckpoint database is freely available at www.tfcheckpoint.org

Contact:  martin.kuiper@ntnu.no

Supplementary information:  Supplementary data are available at Bioinformatics online.
Analysis of base-pairing probabilities of RNA molecules involved in protein–RNA interactions
Authors: Iwakiri Junichi , Kameda Tomoshi , Asai Kiyoshi , Hamada Michiaki
Published: August 2013

Motivation: Understanding the details of protein–RNA interactions is important to reveal the functions of both the RNAs and the proteins. In these interactions, the secondary structures of the RNAs play an important role. Because RNA secondary structures in protein–RNA complexes are variable, considering the ensemble of RNA secondary structures is a useful approach. In particular, recent studies have supported the idea that, in the analysis of RNA secondary structures, the base-pairing probabilities (BPPs) of RNAs (i.e. the probabilities of forming a base pair in the ensemble of RNA secondary structures) provide richer and more robust information about the structures than a single RNA secondary structure, for example, the minimum free energy structure or a snapshot of structures in the Protein Data Bank. However, there has been no investigation of the BPPs in protein–RNA interactions.

Results: In this study, we analyzed BPPs of RNA molecules involved in known protein–RNA complexes in the Protein Data Bank. Our analysis suggests that, in the tertiary structures, the BPPs (which are computed using only sequence information) for unpaired nucleotides with intermolecular hydrogen bonds (hbonds) to amino acids were significantly lower than those for unpaired nucleotides without hbonds. On the other hand, no difference was found between the BPPs for paired nucleotides with and without intermolecular hbonds. Those findings were commonly supported by three probabilistic models, which provide the ensemble of RNA secondary structures, including the McCaskill model based on Turner’s free energy of secondary structures.

Contact:  iwakiri@cb.k.u-tokyo.ac.jp or mhamada@cb.k.u-tokyo.ac.jp

Supplementary information:  Supplementary data are available at Bioinformatics online.
Cutting the first ‘teeth’: a new approach to functional analysis of conodont elements
Authors: Murdock Duncan J. E. , Sansom Ivan J. , Donoghue Philip C. J.
Published: August 2013

The morphological disparity of conodont elements rivals the dentition of all other vertebrates, yet relatively little is known about their functional diversity. Nevertheless, conodonts are an invaluable resource for testing the generality of functional principles derived from vertebrate teeth, and for exploring convergence in a range of food-processing structures. In a few derived conodont taxa, occlusal patterns have been used to derive functional models. However, conodont elements commonly and primitively exhibit comparatively simple coniform morphologies, functional analysis of which has not progressed much beyond speculation based on analogy. We have generated high-resolution tomographic data for each morphotype of the coniform conodontPanderodus acostatus. Using virtual cross sections, it has been possible to characterize changes in physical properties associated with individual element morphology. Subtle changes in cross-sectional profile have profound implications for the functional performance of individual elements and the apparatus as a whole. This study has implications beyond the ecology of a single conodont taxon. It provides a basis for reinterpreting coniform conodont taxonomy (which is based heavily on cross-sectional profiles), in terms of functional performance and ecology, shedding new light on the conodont fossil record. This technique can also be applied to more derived conodont morphologies, as well as analogous dentitions in other vertebrates and invertebrates.
Vicariance across major marine biogeographic barriers: temporal concordance and the relative intensity of hard versus soft barriers
Authors: Cowman Peter F. , Bellwood David R.
Published: August 2013

The marine tropics contain five major biogeographic regions (East Pacific, Atlantic, Indian Ocean, Indo-Australian Archipelago (IAA) and Central Pacific). These regions are separated by both hard and soft barriers. Reconstructing ancestral vicariance, we evaluate the extent of temporal concordance in vicariance events across three major barriers (Terminal Tethyan Event (TTE), Isthmus of Panama (IOP), East Pacific Barrier, EPB) and two incomplete barriers (either side of the IAA) for the Labridae, Pomacentridae and Chaetodontidae. We found a marked lack of temporal congruence within and among the three fish families in vicariance events associated with the EPB, TTE and IOP. Vicariance across hard barriers separating the Atlantic and Indo-Pacific (TTE, IOP) is temporally diffuse, with many vicariance events preceding barrier formation. In marked contrast, soft barriers either side of the IAA hotspot support tightly concordant vicariance events (2.5 Myr on Indian Ocean side; 6 Myr on Central Pacific side). Temporal concordance in vicariance points to large-scale temporally restricted gene flow during the Late Miocene and Pliocene. Despite different and often complex histories, both hard and soft barriers have comparably strong effects on the evolution of coral reef taxa.
ArabidopsisBasic Helix-Loop-Helix Transcription Factors MYC2, MYC3, and MYC4 Regulate Glucosinolate Biosynthesis, Insect Performance, and Feeding Behavior
Authors: Schweizer Fabian , Fernández-Calvo Patricia , Zander Mark , Diez-Diaz Monica , Fonseca Sandra , Glauser Gaétan , Lewsey Mathew G. , Ecker Joseph R. , Solano Roberto , Reymond Philippe
Published: August 2013

Arabidopsis thaliana plants fend off insect attack by constitutive and inducible production of toxic metabolites, such as glucosinolates (GSs). A triple mutant lacking MYC2, MYC3, and MYC4, three basic helix-loop-helix transcription factors that are known to additively control jasmonate-related defense responses, was shown to have a highly reduced expression of GS biosynthesis genes. The myc2 myc3 myc4 (myc234) triple mutant was almost completely devoid of GS and was extremely susceptible to the generalist herbivore Spodoptera littoralis. On the contrary, the specialist Pieris brassicae was unaffected by the presence of GS and preferred to feed on wild-type plants. In addition, lack of GS in myc234 drastically modified S. littoralis feeding behavior. Surprisingly, the expression of MYB factors known to regulate GS biosynthesis genes was not altered in myc234, suggesting that MYC2/MYC3/MYC4 are necessary for direct transcriptional activation of GS biosynthesis genes. To support this, chromatin immunoprecipitation analysis showed that MYC2 binds directly to the promoter of several GS biosynthesis genes in vivo. Furthermore, yeast two-hybrid and pull-down experiments indicated that MYC2/MYC3/MYC4 interact directly with GS-related MYBs. This specific MYC–MYB interaction plays a crucial role in the regulation of defense secondary metabolite production and underlines the importance of GS in shaping plant interactions with adapted and nonadapted herbivores.
Corporate heritage, corporate heritage marketing, and total corporate heritage communications
Authors: Balmer John M.T.
Published: August 2013

Purpose

The purpose of this paper is to advance the general understanding of the corporate heritage domain. The paper seeks to specify the requisites of corporate heritage and to introduce and explicate the corporate heritage marketing and total corporate heritage communications notions.

Design/methodology/approach

As befits an opening article of the first special edition specifically devoted to corporate heritage, this article is largely conceptual in character and draws on the extant literature on corporate heritage brands and identities. In illuminating key points, it also makes reference to extant corporate heritage entities/brands.

Findings

A provisional theory of corporate heritage sustainability is articulated, as is the enumeration of key corporate heritage traits. The notions of corporate heritage marketing and total corporate heritage communications are introduced and articulated. Key corporate heritage traits requisites encompass omni‐temporality; institution trait constancy; external/internal tri‐generational hereditary; augmented role identities; ceaseless multigenerational stakeholder utility and unremitting management tenacity. Corporate heritage marketing consists of eight dimensions: corporate heritage character/communications/covenant/conceptualisations/culture/constituencies/custodianship/context. Total corporate heritage communicates consists of primary/secondary/tertiary and legacy communications.

Practical implications

The paper notes the need for assiduous management attention to be accorded to organisations with a bona‐fide corporate heritage. Managers are custodians – as are organisational members guardians – of a corporate heritage. Corporate heritage institutions because they aresui generisrequire distinct approachesvis‐à‐vistheir preservation and management.

Social implications

Corporate heritage identities and corporate heritage brands confer not only corporate but also temporal, territorial, social, cultural and ancestral identities to multi‐generational groups of customers and other stakeholders. As such, they are of importance not only as corporate entities but also as perennial social identities as well. This is of importance to policy makers, managers and owners of corporate heritage identities and corporate heritage brands.

Originality/value

The unveiling of corporate heritage marketing and of total corporate heritage communications perspective and the articulation of key corporate heritage entity traits is original and is of value to corporate communications/corporate marketing scholars and practitioners alike.
Adding dynamics to core competence concept applications
Authors: Ljungquist Urban
Published: August 2013

Purpose

This paper seeks to enhance practical applications, by refining the original core competence concept to better fit dynamic environments.

Design/methodology/approach

This paper combines theoretical research streams treating core competence and dynamic capability.

Findings

The original core competence concept cannot help managers with today's dynamic business environments. This paper theoretically reviews conceptions of core competence to enhance dynamism and better align theory and practice. The author concludes that a core competence could become more dynamic in three ways, by: balancing itself with the external environment and including external activities and processes; reducing path‐dependency influences; and carefully “orchestrating” resources, by guidance rather than control, to release the inherent potential of project teams.

Research limitations/implications

The author rejuvenates a popular concept by including contemporary, more dynamic considerations; however, his propositions need to be tested empirically.

Practical implications

Three criteria are reformulated to match contemporary dynamism; these are also rephrased to better meet practical applications and take account of the internal sharing and transfer of competencies. This supplements the practitioner's toolbox for managing core competence in a company. For ideal core competence dynamism, managers should selectively incorporate external information and adapt external activities and processes, all to match the existing internal resource base.

Originality/value

This paper incorporates contemporary dynamics in an important strategy concept.