bluuebunny/crossref_metadata_2025 huggingface dataset:
Donor and acceptor doping effects on the electrical conductivity of CaBi2Nb2O9 ceramics
Authors: Chen Huanbei , Guo Xiangxin , Cui Zhonghui , Zhai Jiwei
Published: January 2013

The effects of donor dopants and acceptor dopants (A and B sites) on the resistivity of CaBi2Nb2O9 (CBN) ceramics were studied. The results indicate that the dominant conduction mechanism of pure CBN is p‐type. When the donor doping amount x < 0.05 on A site and x < 0.02 on B site, the resistivity increased with increasing donor doping. With a further increase of donor doping, the resistivity decreased since conductivity mechanism changes from p‐type to n‐type. The resistivity with acceptor doping is decreased at low temperature and equal to the pure CBN ceramic at high temperature since the resistivity of the grain boundary decreases. This work provides a way to obtain high‐resistivity CBN ceramics by appropriate donor doping, which is benefit for use in high‐temperature piezoelectrics.
Bayesian model averaging in astrophysics: a review
Authors: Parkinson David , Liddle Andrew R.
Published: January 2013

We review the use of Bayesian model averaging in astrophysics. We first introduce the statistical basis of Bayesian model selection and model averaging. We discuss methods to calculate the model‐averaged posteriors, including Markov chain Monte Carlo (MCMC), nested sampling, population Monte Carlo, and reversible jump MCMC (RJMCMC). We then review some applications of Bayesian model averaging in astrophysics, including measurements of the dark energy and primordial power spectrum parameters in cosmology, cluster weak lensing, and Sunyaev–Zel'dovich effect data, estimating distances to Cepheids and classifying variable stars. © 2013 Wiley Periodicals, Inc. Statistical Analysis and Data Mining 6: 3–14, 2013
The elephant in the room of dynamic capabilities: Bringing two diverging conversations together
Authors: Peteraf Margaret , Di Stefano Giada , Verona Gianmario
Published: January 2013

A critical issue has been absent from the conversation on dynamic capabilities: the two seminal papers represent not only different but contradictory understandings of the construct's core elements. Here, we explore the reasons for this, using author cocitation analysis to inform our analysis. Our findings suggest that the field is being socially constructed on the basis of two separate domains of knowledge and that underlying structural impediments have impeded dialog across the domains. In light of this evidence, then, we take up the challenge to find a solution to this dilemma. By employing a contingency‐based approach, we show that there are ways to unify the field that rely, paradoxically, on integrating the two contradictory views, while still preserving the assumptions that led to their differences. Copyright © 2013 John Wiley & Sons, Ltd.
Exploration or exploitation? Small firms' alliance strategies with large firms
Authors: Yang Haibin , Zheng Yanfeng , Zhao Xia
Published: January 2013

How do small firms manage their alliance strategies with large firms? This study compares the relative impacts of exploration and exploitation alliances with large firms on small firms' valuation. Integrating the literatures on the exploration/exploitation paradigm and alliance governance, we argue that exploitation alliances with large firms will on average generate higher values for small firms than exploration alliances with large firms due to a heightened risk of appropriation in exploration alliances. However, if small firms can manage their alliances with large firms via proper alliance governance, they will increase their valuations from exploration alliances with large firms. Analyses of the U.S. biopharmaceutical industry from 1984 to 2006 largely support our hypotheses. Copyright © 2013 John Wiley & Sons, Ltd.
Technological overlap, technological capabilities, and resource recombination in technological acquisitions
Authors: Sears Joshua , Hoetker Glenn
Published: January 2013

The performance of technological acquisitions depends heavily on the overlap between the knowledge bases of the target and acquirer. We argue that overlap is best viewed as two distinct constructs: target overlap, the proportion of the target's knowledge base that the acquirer already possesses, and acquirer overlap, the proportion of the acquirer's knowledge base duplicated by the target. Each affects the value created from the firms' technological capabilities differently due to absorptive capacity, knowledge redundancy, and organizational disruption. Further, the low quantity of innovations observed in acquisitions with low target overlap may conceal an offsetting increase in their novelty. Copyright © 2013 John Wiley & Sons, Ltd.
On the assessment of multivariate and multisite measurement systems
Authors: Scagliarini Michele
Published: January 2013

The multivariate Measurement Systems Analysis (MSA) approval criteria proposed in literature are specifically designed for assessing measurement systems made up of a single instrument. Therefore, they may encounter difficulties in assessing multisite measurement systems where there are multiple instruments in parallel. In this work, we propose a method for assessing such complex measurement systems. Since a key assumption in multisite measurement systems is that all instruments are expected to have the same level of precision, we base our proposal on the comparison of the precisions of multivariate instruments by means of a statistical test. A simulation study is performed in order to evaluate the performances of the proposed method. The results show that the illustrated approach is effective for assessing complex measurement systems and can be useful for reducing the costs for performing multivariate MSA. Copyright © 2013 John Wiley & Sons Ltd
Reactivity Studies of LAlH2 [L = HC(CMeNAr)2, Ar = 2, 6‐iPr2C6H3] with 2‐[(2‐Hydroxybenzylidene)amino]‐3‐mercapto­propionic Acid and Benzene‐1, 2‐diamine
Authors: Ma Xiaoli , Hao Pengfei , Li Jie , Roesky Herbert W. , Yang Zhi
Published: January 2013

The reaction of LAlH2 [L = HC(CMeNAr)2, Ar = 2, 6‐iPr2C6H3] (1) with 2‐[(2‐hydroxybenzylidene)amino]‐3‐mercaptopropionic acid and benzene‐1, 2‐diamine resulted in the compounds LAl[(μ‐O)(o‐C6H4)][(μ‐O)(COCHCH2SH)](NCH) (2) and LAl(μ‐NH)2(o‐C6H4) (3), respectively. Compound 2 is an unusual aluminum Schiff base, which exhibits a C3NAlO six‐ and a C2NAlO five‐membered ring, which share the same Al←N coordinate bond. Moreover the aluminum atom is five‐coordinate and functions as the center of the three heterocycles. Compound 3 features an organic‐inorganic hybrid containing a C2N2Al five‐membered ring. Complexes 2 and 3 were characterized by 1H NMR, elemental analysis, and single‐crystal X‐ray diffraction studies.
Scrutinizing the Higgs signal and background in the 2e2μ golden channel
Authors: Chen Yi , Tran Nhan , Vega-Morales Roberto
Published: January 2013

Abstract

Kinematic distributions in the decays of the newly discovered resonance to four leptons are a powerful probe of the tensor structure of its couplings to electroweak gauge bosons. We present analytic calculations for both signal and background of the fully differential cross section for the ‘Golden Channel’ e
+
e
−
μ
+
μ
− final state. We include all interference effects between intermediate gauge bosons and allow them to be on- or off-shell. For the signal we compute the fully differential decay width for general scalar couplings to ZZ,γγ,andZγ. For the background we compute the leading order fully differential cross section for q q annihilation into Z and γ gauge bosons, including the contribution from the resonant Z → 2e2μ process. We also present singly and doubly differential projections and study the interference effects on the differential spectra. These expressions can be used in a variety of ways to uncover the nature of the newly discovered resonance or any new scalars decaying to neutral gauge bosons which might be discovered in the future.
Limit cycles and conformal invariance
Authors: Fortin Jean-François , Grinstein Benjamín , Stergiou Andreas
Published: January 2013

Abstract

There is a widely held belief that conformal field theories (CFTs) require zero beta functions. Nevertheless, the work of Jack and Osborn implies that the beta functions are not actually the quantites that decide conformality, but until recently no such behavior had been exhibited. Our recent work has led to the discovery of CFTs with nonzero beta functions, more precisely CFTs that live on recurrent trajectories, e.g., limit cycles, of the beta-function vector field. To demonstrate this we study the S function of Jack and Osborn. We use Weyl consistency conditions to show that it vanishes at fixed points and agrees with the generator Q of limit cycles on them. Moreover, we compute S to third order in perturbation theory, and explicitly verify that it agrees with our previous determinations of Q. A byproduct of our analysis is that, in perturbation theory, unitarity and scale invariance imply conformal invariance in four-dimensional quantum field theories. Finally, we study some properties of these new, “cyclic” CFTs, and point out that the a-theorem still governs the asymptotic behavior of renormalization-group flows.
Diagnosing mucopolysaccharidosis IVA
Authors: Wood Timothy C. , Harvey Katie , Beck Michael , Burin Maira Graeff , Chien Yin‐Hsiu , Church Heather J. , D'Almeida Vânia , van Diggelen Otto P. , Fietz Michael , Giugliani Roberto , Harmatz Paul , Hawley Sara M. , Hwu Wuh‐Liang , Ketteridge David , Lukacs Zoltan , Miller Nicole , Pasquali Marzia , Schenone Andrea , Thompson Jerry N. , Tylee Karen , Yu Chunli , Hendriksz Christian J.
Published: January 2013

Mucopolysaccharidosis IVA (MPS IVA; Morquio A syndrome) is an autosomal recessive lysosomal storage disorder resulting from a deficiency of N‐acetylgalactosamine‐6‐sulfate sulfatase (GALNS) activity. Diagnosis can be challenging and requires agreement of clinical, radiographic, and laboratory findings. A group of biochemical genetics laboratory directors and clinicians involved in the diagnosis of MPS IVA, convened by BioMarin Pharmaceutical Inc., met to develop recommendations for diagnosis. The following conclusions were reached. Due to the wide variation and subtleties of radiographic findings, imaging of multiple body regions is recommended. Urinary glycosaminoglycan analysis is particularly problematic for MPS IVA and it is strongly recommended to proceed to enzyme activity testing even if urine appears normal when there is clinical suspicion of MPS IVA. Enzyme activity testing of GALNS is essential in diagnosing MPS IVA. Additional analyses to confirm sample integrity and rule out MPS IVB, multiple sulfatase deficiency, and mucolipidoses types II/III are critical as part of enzyme activity testing. Leukocytes or cultured dermal fibroblasts are strongly recommended for enzyme activity testing to confirm screening results. Molecular testing may also be used to confirm the diagnosis in many patients. However, two known or probable causative mutations may not be identified in all cases of MPS IVA. A diagnostic testing algorithm is presented which attempts to streamline this complex testing process.
An evaluation of supracondylar humerus fractures: Is there a correlation between postponing treatment and the need for open surgical intervention?
Authors: Kronner John M. , Legakis Julie E. , Kovacevic Natalia , Thomas Ronald L. , Reynolds Richard A. K. , Jones Eric T.
Published: January 2013

Purpose

The goal of this study was to evaluate the treatment and recovery of patients treated for Gartland type III supracondylar humerus fractures in order to determine if postponing treatment leads to a higher rate of open surgical treatment or complications.

Methods

A retrospective study was conducted examining the medical records of children with Gartland type III supracondylar humerus fractures at our institution for a two-year period. The patients included in the study were treated with closed reduction and percutaneous pinning (CRPP) or open reduction and internal fixation (ORIF).

Results

After exclusions, 134 patients were included in the study, with an average age of 5.6 years. The patients were grouped according to whether their treatment was postponed (39.6 %) or immediate (60.4 %). The majority of all patients were treated using CRPP: 46 (86.8 %) of the postponed patients and 75 (92.6 %) of the immediate patients. Very few postsurgical complications occurred in the patients; there was only one (1.6 %) case of iatrogenic nerve injury in a postponed patient as well as four (3.8 %) cases of loss of carrying angle: one (2.3 %) in postponed patients and three (4.8 %) in immediate patients.

Conclusions

Postponing treatment of type III supracondylar humerus fractures in children did not lead to an increase in open surgical treatment; nor did it lead to an increase in complications.
Towards organizational development for sustainable high-quality medical
teaching
Authors: Engbers Rik , Stuyt Paul M. J. , Fluit Cornelia R. M. G. , Bolhuis Sanneke , De Caluwe´ Le´on I. A.
Published: January 2013

Literature shows that faculty development programmes are not organizationally
embedded in academic hospitals. This leaves medical teaching a low and informal status.
The purpose of this article is to explore how organizational literature can strengthen
our understanding of embedding faculty development in organizational development, and to
provide a useful example of organizational development with regards to medical teaching
and faculty development. Constructing a framework for organizational development from
the literature, based on expert brainstorming. This framework is applied to a case
study. A framework for organizational development is described. Applied in a context of
medical teaching, these organizational insights show the process (and progress) of
embedding faculty development in organizational development. Organizational development
is a necessary condition for assuring sustainable faculty development for high-quality
medical teaching. Organizational policies can only work in an organization that is
developing. Recommendations for further development and future research are
discussed.
Effects of Bai‐Hu decoction on fever induced by lipopolysaccharide
Authors: Jia Li‐Long , Li Ran , Ma Ji , Fan Ying , Li Hai‐Bo
Published: January 2013

This study was designed to investigate the antifebrile effect and mechanisms of Bai‐Hu decoction (BHD), a traditional Chinese medical (TCM) prescription. The rabbits used in this study received an intravenous injection of lipopolysaccharide (LPS) after being orally administered with BHD, ibuprofen, or saline, and their rectal temperatures were monitored by a copper–constantan thermocouple. Concentrations of interleukin‐1 beta (IL‐1β) and tumor necrosis factor alpha (TNF‐α) in serum and hypothalamus were assayed using the commercially available rabbit IL‐1β and TNF‐α enzyme‐linked immunosorbent assay kits following the manufacturer's instructions. The BHD treatment group exhibited a significant fall in body temperature in both peaks compared with the LPS group (p < 0.05). BHD reduced the concentrations of IL‐1β and TNF‐α in serum, and of TNF‐α in hypothalamus to control the febrile responses at 1 hour. Besides the levels of IL‐1β in hypothalamus and serum, the concentration of TNF‐α in hypothalamus was decreased remarkably in the BHD group than in the LPS group at 3 hours. The main findings, the partial mechanisms of BHD in reducing biphasic fever elicited by LPS, were that treatments with the crude extract of BHD could remarkably reduce the increased concentrations of IL‐1β and TNF‐α, not only in serum but also in hypothalamus. The results indicated that BHD would be a valuable candidate for further investigation as a traditional antifebrile and anti‐inflammatory natural drug.
Do FOMC minutes matter to markets? An intraday analysis of FOMC minutes releases on individual equity volatility and returns
Authors: Jubinski Daniel , Tomljanovich Marc
Published: January 2013

This paper examines the 2006 to 2007 time period to determine the extent to which the release of the Federal Reserve minutes affects equity volatility and returns for 2832 individual firms. Using intraday data, we find that equity returns are essentially unaffected by FOMC minutes releases. We do find evidence of volatility effects, in that conditional volatility is lower prior to the minutes release and higher after the minutes release on release days, relative to a “control” day one week prior to the release date. These differences manifest at the 2:00–2:05 pm interval, and generally dissipate within 15 min. Consistent with previous literature, we also find evidence of both industry‐specific and firm size effects in our data. Finally, we see that volatility is higher (lower) when the minutes are released after the Federal Reserve engages in restrictive (expansionary) monetary policy. Our results are robust to a variety of different definitions of the “control” dates, as well as differing industry definitions.
Morphological consequences of lateral outfracture of the inferior turbinate
Authors: Hanna B C , Bailie N , Gallagher G , Cole J
Published: January 2013

Objective:

We report three cases of lateral outfracture of the inferior turbinate, which demonstrate a range of changes in the size, position and shape of the inferior turbinate.

Method:

During a study of the validity of computer modelling of nasal airflow, computed tomography scans of the noses of patients who had undergone lateral outfracture of the inferior turbinate were collected. The pre-operative scan was compared with the post-operative scan six weeks later.

Results:

In one patient, there was only a small lateral displacement of the inferior turbinate. In the other two cases, appreciable reduction in the volume of one inferior turbinate was noted, in addition to minor changes in the shape.

Conclusion:

Lateral outfracture of the inferior turbinate produces varied and inconsistent changes in morphology which may affect the shape, size and position of the turbinate.
Medicine Reading Literature: the Paradigm of Degeneration
Authors: Arampatzidou Lena
Published: January 2013

This article is part of a larger project on the interaction between Natural/Life Sciences and Literature, and is a first attempt to scout the area through concentrating onDegeneration, a book that sees Literature through the eyes of Medicine. Max Nordau, the author of the book, was a turn-of-the-twentieth-century German physician who read contemporary movements in Art and Literature as Disease. He was an adversary of pre-modernist and modernist movements such as aestheticism, decadence, impressionism, and so on, and failed to recognize their avant-garde character. The article examines how Nordau reads certain features of literary texts and works of art which he cannot understand as symptoms of the malfunctioning of the nervous system of the painters and writers concerned. Moving from the body of the text to the body of the artist, Nordau reads particular artistic features as signs of bodily disease of the artists, and he does so by opposing the rationalist discourse of Medicine to the figurative language of Literature.
The Role of the National Problem in the Disintegration of the Soviet Union
Authors: Shinar Chaim
Published: January 2013

‘The Soviet Union, like the United States, was a country established to serve and promote a political idea, not to be a state for nations. The United States was founded in order to be a modern democratic polity; the Soviet Union in order to promote Marxism-Leninism. The Soviet Union thus began as a ‘modern,’ post-imperialist state. The cement holding the state together was a compound of ideology, a hierarchical, disciplinary party, charismatic leadership, and external treats. [In the 80s] this cement was crumbling… [The Soviet] state had lost its raison d’être and the people turned to the traditional and conventional basis of the state – that is, the nation. But since this was a multinational state – and unlike the multiethnic United States, most peoples in the USSR have distinct languages and territories of their own – [they returned to them to establish independent states.]’1
The Council of Europe, Rights and Political Authority
Authors: Sithole Kundai
Published: January 2013

This paper examines the importance of human rights protection – in particular the European Convention on Human Rights – to the Council of Europe's survival as a political authority. Its underlying premise is that the proliferation of regional organisations in Europe in post-war Europe, and the creation of the Communities in 1958, contributed to a loss of a sense of purpose as to the Council of Europe's role in post-war Europe. Initial attempts to widen the scope of its political authority in relation to the Member States and other regional organisations were unsuccessful. It was, therefore, necessary for the Council of Europe to consolidate its existing mandate in ensuring the region's democratic security through human rights protection. Thus, led by its Parliamentary Assembly, Council of Europe institutions have, since 1949, provided the Member States with the necessary regional fora for examining and promulgating regional human rights legislation, such as the European Convention on Human Rights and its two additional protocols abolishing the death penalty.
Carl Schmitt and the analogy between constitutional and international law: Are constitutional and international law inherently political?
Authors: VINX LARS
Published: January 2013

According to Carl Schmitt, constitutional law and international law are analogous in that they are both forms of political law. Schmitt concludes that neither is open to legitimate judicial enforcement. This paper critically explores Schmitt’s analogy between constitutional and international law. It argues that the analogy can be turned against Schmitt and contemporary sceptics about international law: Since we no longer have any reason to deny the judicial enforceability of domestic constitutional law, the analogy now suggests that there is no reason to think that legitimate judicial enforcement of international law is impossible.
Conflicts of rights in international human rights: A meta-rule analysis
Authors: AROSEMENA GUSTAVO
Published: January 2013

This study is an analytical account of the phenomenon of conflicts of rights, tailored to the context of international human rights law. It addresses the nature of conflicts of rights, the relationship between conflicts of rights and the extent and scope of the rights catalogue and the methods used to resolve conflicts. It is structured around the notion of a meta-rule. It argues that a conflict of rights can only be resolved ‘legally’ through the application of a rule that guides the decision maker to a solution. The study addresses the suitability and justification of such rules.
Contesting constitutionalism: Constitutional discourse at the WTO
Authors: LAWRENCE JESSICA C
Published: January 2013

Debates about ‘constitutionalism’ have become an important trend in WTO scholarship. Despite over two decades of interest, however, a coherent definition of the term and its content remain out of reach. This paper argues that ‘constitutionalism’ should be approached not as something that can be measured or assessed empirically, but rather as a ‘discursive contest’: a debate in which participants intervene on behalf of particular understandings of how the system does or should operate. Approaching constitutionalism as a discursive contest adds to the literature by shifting the focus to an analysis of how ‘constitutional talk’ produces knowledge about the WTO, and how this knowledge in turn structures perceptions about the way government works and the possibilities for action. Providing examples from scholarly debates and WTO practice, the article aims to make concrete the relationship between truth and government and the implications of discursive contests over constitutionalism in the field of WTO law.
What’s in a Face?
Authors: Duval Elizabeth R. , Moser Jason S. , Huppert Jonathan D. , Simons Robert F.
Published: January 2013

Morphed faces depicting varying degrees of affect expression can be used to investigate the processing of ambiguous and thus more ecologically valid facial stimuli. Event-related brain potentials (ERPs) were measured while participants viewed a series of faces ranging in 10% increments from prototypically happy to prototypically neutral to prototypically angry. Results revealed that the late positive potential (LPP) – an ERP reflecting later stages of stimulus processing – followed the degree of expression of facial affect such that faces depicting a greater amount of affect elicited larger LPPs as compared to faces depicting less affect. The enhanced LPP to faces depicting greater amounts of affect was also more sustained for angry compared to happy faces – in general, angry faces elicited larger LPPs. Overall, these results demonstrate the sensitivity of the LPP to more ecologically valid facial expressions and thus the visual system’s finely tuned discriminability of important social signals.
A global perspective on marine photosynthetic picoeukaryote community structure
Authors: Kirkham Amy R , Lepère Cécile , Jardillier Ludwig E , Not Fabrice , Bouman Heather , Mead Andrew , Scanlan David J
Published: January 2013

A central goal in ecology is to understand the factors affecting the temporal dynamics and spatial distribution of microorganisms and the underlying processes causing differences in community structure and composition. However, little is known in this respect for photosynthetic picoeukaryotes (PPEs), algae that are now recognised as major players in marine CO2 fixation. Here, we analysed dot blot hybridisation and cloning–sequencing data, using the plastid-encoded 16S rRNA gene, from seven research cruises that encompassed all four ocean biomes. We provide insights into global abundance, α- and β-diversity distribution and the environmental factors shaping PPE community structure and composition. At the class level, the most commonly encountered PPEs were Prymnesiophyceae and Chrysophyceae. These taxa displayed complementary distribution patterns, with peak abundances of Prymnesiophyceae and Chrysophyceae in waters of high (25:1) or low (12:1) nitrogen:phosphorus (N:P) ratio, respectively. Significant differences in phylogenetic composition of PPEs were demonstrated for higher taxonomic levels between ocean basins, using Unifrac analyses of clone library sequence data. Differences in composition were generally greater between basins (interbasins) than within a basin (intrabasin). These differences were primarily linked to taxonomic variation in the composition of Prymnesiophyceae and Prasinophyceae whereas Chrysophyceae were phylogenetically similar in all libraries. These data provide better knowledge of PPE community structure across the world ocean and are crucial in assessing their evolution and contribution to CO2 fixation, especially in the context of global climate change.
Aminolaevulinic acid synthase of Rhodobacter capsulatus: high-resolution kinetic investigation of the structural basis for substrate binding and catalysis
Authors: Kaufholz Anna-Lena , Hunter Gregory A. , Ferreira Gloria C. , Lendrihas Thomas , Hering Vanessa , Layer Gunhild , Jahn Martina , Jahn Dieter
Published: January 2013

The first enzyme of haem biosynthesis, ALAS (5-aminolaevulinic acid synthase), catalyses the pyridoxal 5′-phosphate-dependent condensation of glycine and succinyl-CoA to 5-aminolaevulinic acid, CO2 and CoA. The crystal structure of Rhodobacter capsulatus ALAS provides the first snapshots of the structural basis for substrate binding and catalysis. To elucidate the functional role of single amino acid residues in the active site for substrate discrimination, substrate positioning, catalysis and structural protein rearrangements, multiple ALAS variants were generated. The quinonoid intermediates I and II were visualized in single turnover experiments, indicating the presence of an α-amino-β-oxoadipate intermediate. Further evidence was obtained by the pH-dependent formation of quinonoid II from the product 5-aminolaevulinic acid. The function of Arg21, Thr83, Asn85 and Ile86, all involved in the co-ordination of the succinyl-CoA substrate carboxy group, were analysed kinetically. Arg21, Thr83and Ile86, all of which are located in the second subunit to the intersubunit active site, were found to be essential. Their location in the second subunit provides the basis for the required structural dynamics during the complex condensation of both substrates. Utilization of L-alanine by the ALAS variant T83S indicated the importance of this residue for the selectiveness of binding with the glycine substrate compared with related amino acids. Asn85 was found to be solely important for succinyl-CoA substrate recognition and selectiveness of binding. The results of the present study provide a novel dynamic view on the structural basis of ALAS substrate-binding and catalysis.
Nitrogen monoxide inhibits haem synthesis in mouse reticulocytes
Authors: Mikhael Marc R. , Soe-Lin Shan , Apte Sameer , Ponka Prem
Published: January 2013

AI (anaemia of inflammation) often manifests in patients with chronic immune activation due to cancer, chronic infections, autoimmune disorders, rheumatoid arthritis and other diseases. The pathogenesis of AI is complex and involves cytokine-mediated inhibition of erythropoiesis, insufficient erythropoietin production and diminished sensitivity of erythroid progenitors to this hormone, and retention of iron in haemoglobin-processing macrophages. NO (nitric oxide) is a gaseous molecule produced by activated macrophages that has been identified as having numerous effects on iron metabolism. In the present study, we explore the possibility that NO affects iron metabolism in reticulocytes and our results suggest that NO may also contribute to AI. We treated reticulocytes with the NO donor SNP (sodium nitroprusside). The results indicate that NO inhibits haem synthesis dramatically and rapidly at the level of erythroid-specific 5-aminolaevulinic acid synthase 2, which catalyses the first step of haem synthesis in erythroid cells. We also show that NO leads to the inhibition of iron uptake via the Tf (transferrin)–Tf receptor pathway. In addition, NO also causes an increase in eIF2α (eukaryotic initiation factor 2α) phosphorylation levels and decreases globin translation. The profound impairment of haem synthesis, iron uptake and globin translation in reticulocytes by NO raises the possibility that this gas may also contribute to AI.
Exogenous delivery of chaperonin subunit fragment ApiCCT1 modulates mutant Huntingtin cellular phenotypes
Authors: Sontag Emily M. , Joachimiak Lukasz A. , Tan Zhiqun , Tomlinson Anthony , Housman David E. , Glabe Charles G. , Potkin Steven G. , Frydman Judith , Thompson Leslie M.
Published: January 2013

Aggregation of misfolded proteins is characteristic of a number of neurodegenerative diseases, including Huntington disease (HD). The CCT/TRiC (chaperonin containing TCP-1/TCP-1 ring) chaperonin complex can inhibit aggregation and cellular toxicity induced by expanded repeat Huntingtin (mHtt) fragments. The substrate-binding apical domain of CCT/TRiC subunit CCT1, ApiCCT1, is sufficient to inhibit aggregation of expanded repeat mHtt fragments in vitro, providing therapeutic promise for HD. However, a key hurdle in considering ApiCCT1 as a potential treatment is in delivery. Because ApiCCT1 has a region of similarity to the HIV Tat protein cell-transduction domain, we tested whether recombinant ApiCCT1 (ApiCCT1r) protein could enter cells following exogenous delivery and modulate an established panel of mHtt-mediated cell-based phenotypes. Cell fractionation studies demonstrate that exogenous ApiCCT1rcan penetrate cell membranes and can localize to the nucleus, consistent with a strategy that can target both cytosolic and nuclear pathogenic events in HD. ApiCCT1rapplication does indeed modulate HD cellular phenotypes by decreasing formation of visible inclusions, fibrillar oligomers, and insoluble mHtt derived from expression of a truncated mHtt exon 1 fragment. ApiCCT1ralso delays the onset of inclusion body formation as visualized via live imaging. ApiCCT1rreduces mHtt-mediated toxicity in immortalized striatal cells derived from full-length knock-in HD mice, suggesting that therapeutic benefit may extend beyond effects on aggregation. These studies provide the basis for a potentially robust and unique therapeutic strategy to target mHtt-mediated protein pathogenesis.
Intermediate filament-associated cytolinker plectin 1c destabilizes microtubules in keratinocytes
Authors: Valencia Rocio G. , Walko Gernot , Janda Lubomir , Novacek Jirka , Mihailovska Eva , Reipert Siegfried , Andrä-Marobela Kerstin , Wiche Gerhard
Published: January 2013

The transition of microtubules (MTs) from an assembled to a disassembled state plays an essential role in several cellular functions. While MT dynamics are often linked to those of actin filaments, little is known about whether intermediate filaments (IFs) have an influence on MT dynamics. We show here that plectin 1c (P1c), one of the multiple isoforms of the IF-associated cytolinker protein plectin, acts as an MT destabilizer. We found that MTs in P1c-deficient (P1c−/−) keratinocytes are more resistant toward nocodazole-induced disassembly and display increased acetylation. In addition, live imaging of MTs in P1c−/−, as well as in plectin-null, cells revealed decreased MT dynamics. Increased MT stability due to P1c deficiency led to changes in cell shape, increased velocity but loss of directionality of migration, smaller-sized focal adhesions, higher glucose uptake, and mitotic spindle aberrations combined with reduced growth rates of cells. On the basis of ex vivo and in vitro experimental approaches, we suggest a mechanism for MT destabilization in which isoform-specific binding of P1c to MTs antagonizes the MT-stabilizing and assembly-promoting function of MT-associated proteins through an inhibitory function exerted by plectin's SH3 domain. Our results open new perspectives on cytolinker-coordinated IF-MT interaction and its physiological significance.
Phosphorylation on Ser-279 and Ser-282 of connexin43 regulates endocytosis and gap junction assembly in pancreatic cancer cells
Authors: Johnson Kristen E. , Mitra Shalini , Katoch Parul , Kelsey Linda S. , Johnson Keith R. , Mehta Parmender P.
Published: January 2013

The molecular mechanisms regulating the assembly of connexins (Cxs) into gap junctions are poorly understood. Using human pancreatic tumor cell lines BxPC3 and Capan-1, which express Cx26 and Cx43, we show that, upon arrival at the cell surface, the assembly of Cx43 is impaired. Connexin43 fails to assemble, because it is internalized by clathrin-mediated endocytosis. Assembly is restored upon expressing a sorting-motif mutant of Cx43, which does not interact with the AP2 complex, and by expressing mutants that cannot be phosphorylated on Ser-279 and Ser-282. The mutants restore assembly by preventing clathrin-mediated endocytosis of Cx43. Our results also document that the sorting-motif mutant is assembled into gap junctions in cells in which the expression of endogenous Cx43 has been knocked down. Remarkably, Cx43 mutants that cannot be phosphorylated on Ser-279 or Ser-282 are assembled into gap junctions only when connexons are composed of Cx43 forms that can be phosphorylated on these serines and forms in which phosphorylation on these serines is abolished. Based on the subcellular fate of Cx43 in single and contacting cells, our results document that the endocytic itinerary of Cx43 is altered upon cell–cell contact, which causes Cx43 to traffic by EEA1-negative endosomes en route to lysosomes. Our results further show that gap-junctional plaques formed of a sorting motif–deficient mutant of Cx43, which is unable to be internalized by the clathrin-mediated pathway, are predominantly endocytosed in the form of annular junctions. Thus the differential phosphorylation of Cx43 on Ser-279 and Ser-282 is fine-tuned to control Cx43’s endocytosis and assembly into gap junctions.
akirinis required for diakinesis bivalent structure and synaptonemal complex disassembly at meiotic prophase I
Authors: Clemons Amy M. , Brockway Heather M. , Yin Yizhi , Kasinathan Bhavatharini , Butterfield Yaron S. , Jones Steven J. M. , Colaiácovo Monica P. , Smolikove Sarit
Published: January 2013

During meiosis, evolutionarily conserved mechanisms regulate chromosome remodeling, leading to the formation of a tight bivalent structure. This bivalent, a linked pair of homologous chromosomes, is essential for proper chromosome segregation in meiosis. The formation of a tight bivalent involves chromosome condensation and restructuring around the crossover. The synaptonemal complex (SC), which mediates homologous chromosome association before crossover formation, disassembles concurrently with increased condensation during bivalent remodeling. Both chromosome condensation and SC disassembly are likely critical steps in acquiring functional bivalent structure. The mechanisms controlling SC disassembly, however, remain unclear. Here we identify akir-1 as a gene involved in key events of meiotic prophase I in Caenorhabditis elegans. AKIR-1 is a protein conserved among metazoans that lacks any previously known function in meiosis. We show that akir-1 mutants exhibit severe meiotic defects in late prophase I, including improper disassembly of the SC and aberrant chromosome condensation, independently of the condensin complexes. These late-prophase defects then lead to aberrant reconfiguring of the bivalent. The meiotic divisions are delayed in akir-1 mutants and are accompanied by lagging chromosomes. Our analysis therefore provides evidence for an important role of proper SC disassembly in configuring a functional bivalent structure.
Assembly in G1 phase and long-term stability are unique intrinsic features of CENP-A nucleosomes
Authors: Bodor Dani L. , Valente Luis P. , Mata João F. , Black Ben E. , Jansen Lars E. T.
Published: January 2013

Centromeres are the site of kinetochore formation during mitosis. Centromere protein A (CENP-A), the centromere-specific histone H3 variant, is essential for the epigenetic maintenance of centromere position. Previously we showed that newly synthesized CENP-A is targeted to centromeres exclusively during early G1 phase and is subsequently maintained across mitotic divisions. Using SNAP-based fluorescent pulse labeling, we now demonstrate that cell cycle–restricted chromatin assembly at centromeres is unique to CENP-A nucleosomes and does not involve assembly of other H3 variants. Strikingly, stable retention is restricted to the CENP-A/H4 core of the nucleosome, which we find to outlast general chromatin across several cell divisions. We further show that cell cycle timing of CENP-A assembly is independent of centromeric DNA sequences and instead is mediated by the CENP-A targeting domain. Unexpectedly, this domain also induces stable transmission of centromeric nucleosomes, independent of the CENP-A deposition factor HJURP. This demonstrates that intrinsic properties of the CENP-A protein direct its cell cycle–restricted assembly and induces quantitative mitotic transmission of the CENP-A/H4 nucleosome core, ensuring long-term stability and epigenetic maintenance of centromere position.
MosaicFinder: identification of fused gene families in sequence similarity networks
Authors: Jachiet Pierre-Alain , Pogorelcnik Romain , Berry Anne , Lopez Philippe , Bapteste Eric
Published: January 2013

Motivation: Gene fusion is an important evolutionary process. It can yield valuable information to infer the interactions and functions of proteins. Fused genes have been identified as non-transitive patterns of similarity in triplets of genes. To be computationally tractable, this approach usually imposes an a priori distinction between a dataset in which fused genes are searched for, and a dataset that may have provided genetic material for fusion. This reduces the ‘genetic space’ in which fusion can be discovered, as only a subset of triplets of genes is investigated. Moreover, this approach may have a high–false-positive rate, and it does not identify gene families descending from a common fusion event.

Results: We represent similarities between sequences as a network. This leads to an efficient formulation of previous methods of fused gene identification, which we implemented in the Python program FusedTriplets. Furthermore, we propose a new characterization of families of fused genes, as clique minimal separators of the sequence similarity network. This well-studied graph topology provides a robust and fast method of detection, well suited for automatic analyses of big datasets. We implemented this method in the C++ program MosaicFinder, which additionally uses local alignments to discard false-positive candidates and indicates potential fusion points. The grouping into families will help distinguish sequencing or prediction errors from real biological fusions, and it will yield additional insight into the function and history of fused genes.

Availability: FusedTriplets and MosaicFinder are published under the GPL license and are freely available with their source code at this address: http://sourceforge.net/projects/mosaicfinder.

Contact: pogorelc@isima.fr

Supplementary information: Supplementary data are available at Bioinformatics online.
Phantom energy and the Cosmic Horizon: Rh is still not a horizon!
Authors: Lewis Geraint F.
Published: January 2013

There has been a recent spate of papers on the Cosmic Horizon, an apparently fundamental, although unrecognized, property of the universe. The misunderstanding of this horizon, it is claimed, demonstrates that our determination of the cosmological makeup of the universe is incorrect, although several papers have pointed out key flaws in these arguments. Here, we identify additional flaws in the most recent claims of the properties of the Cosmic Horizon in the presence of phantom energy, simply demonstrating that it does not act as a horizon, and that its limiting of our view of the universe is a trivial statement.
Monopolizing Violence and Consolidating Power*
Authors: Powell Robert
Published: January 2013

Governments in weak states often face an armed opposition and have to decide whether to try to accommodate and contain that adversary or to try to consolidate power and monopolize violence by disarming it. When and why do governments choose to consolidate power and monopolize violence? How fast do they try to consolidate power? When does this lead to costly fighting rather than to efforts to eliminate the opposition by buying it off? We study an infinite-horizon model in which the government in each period decides how much to offer the opposition and the rate at which it tries to consolidate its power. The opposition can accept the offer and thereby acquiesce to the government’s efforts to consolidate, or it can fight in an attempt to disrupt those efforts. In equilibrium, the government always tries to monopolize violence when it has “coercive power” against the opposition where, roughly, coercive power is the ability to weaken the opposition by lowering its payoff to fighting. Whether the government consolidates peacefully or through costly fighting depends on the size of any “contingent spoils,” which are benefits that begin to accrue from an increase in economic activity resulting from the monopolization of violence and the higher level of security that comes with it. When contingent spoils are small, the government buys the opposition off and eliminates it as fast as is peacefully possible. When contingent spoils are large, the government tries to monopolize violence by defeating the opposition militarily.
Impact of Iyengar Yoga on Quality of Life in Young Women With Rheumatoid Arthritis
Authors: Evans Subhadra , Moieni Mona , Lung Kirsten , Tsao Jennie , Sternlieb Beth , Taylor Mihaela , Zeltzer Lonnie
Published: January 2013

Objective:

Rheumatoid arthritis (RA) is a chronic, disabling disease that can greatly compromise health-related quality of life (HRQoL). The aim of this study was to assess the impact of a 6-week twice/week Iyengar yoga program on HRQoL of young adults with RA compared with a usual-care waitlist control group.

Methods:

The program was designed to improve the primary outcome of HRQoL including pain and disability and psychological functioning in patients. Assessments were collected pretreatment, posttreatment, and at 2 months after treatment. Weekly ratings of anxiety, depression, pain, and sleep were also recorded. A total of 26 participants completed the intervention (yoga=11; usual-care waitlist=15). All participants were female (mean age=28 y).

Results:

Overall attrition was low at 15%. On average, women in the yoga group attended 96% of the yoga classes. No adverse events were reported. Relative to the usual-care waitlist, women assigned to the yoga program showed significantly greater improvement on standardized measures of HRQoL, pain disability, general health, mood, fatigue, acceptance of chronic pain, and self-efficacy regarding pain at posttreatment. Almost half of the yoga group reported clinically meaningful symptom improvement. Analysis of the uncontrolled effects and maintenance of treatment effects showed improvements in HRQoL general health, pain disability, and weekly ratings of pain, anxiety, and depression were maintained at follow-up.

Conclusions:

The findings suggest that a brief Iyengar yoga intervention is a feasible and safe adjunctive treatment for young people with RA, leading to HRQoL, pain disability, fatigue, and mood benefits. Moreover, improvements in quality of life, pain disability, and mood persisted at the 2-month follow-up.
The MMP1 rs1799750 2G Allele is Associated With Increased Low Back Pain, Sciatica, and Disability After Lumbar Disk Herniation
Authors: Jacobsen Line M. , Schistad Elina I. , Storesund Anette , Pedersen Linda M. , Espeland Ansgar , Rygh Lars J. , Røe Cecilie , Gjerstad Johannes
Published: January 2013

Objectives:

Previous studies indicate that genetic variants in genes encoding proteins like matrix metalloproteinase (MMP) enzymes may affect degeneration of the intervertebral disk. One such genetic variant is a single nucleotide polymorphism insertion in the promoter region of the MMP1 gene, that is, the MMP1 rs1799750 2G allele, which increases the MMP1 expression in vitro. In this study, we examined whether the MMP1 rs1799750 2G allele might be associated with disk degeneration and clinical outcome after lumbar disk herniation.

Materials and Methods:

A total of 260 patients with lumbar disk herniation and sciatic pain were included in this study and genotyped for the MMP1 rs1799750 2G allele.

Results:

The present data showed no differences in the frequency of the MMP1 2G allele in patients recently diagnosed with disk herniation compared with pain-free controls. Moreover, in the patients, the MMP1 2G allele was not directly related to the disk degeneration. However, our data demonstrated that the MMP1 2G allele was associated with both pain and disability, that is, increased visual analog scale score, McGill Pain Questionnaire score, and Oswestry Disability Index score. Clearly, the patients homozygous for the 2G allele had more pain and reduced function compared with those carrying the 1G allele.

Discussions:

Our findings suggest that the MMP1 rs1799750 2G/2G genotype may contribute to low back pain, sciatica, and disability after lumbar disk herniation.