bluuebunny/crossref_metadata_2025 huggingface dataset:
Expedient access to substituted 3-amino-2-cyclopentenones by dirhodium-catalyzed [3+2]-annulation of silylated ketene imines and enoldiazoacetates
Authors: Xu Xichen , Leszczynski John S. , Mason Savannah M. , Zavalij Peter Y. , Doyle Michael P.
Published: January 2014

3-Amino-2-cyclopentenones with a quaternary carbon at the 4-position from formal [3+2]-cycloaddition of silylated ketene imines (SKIs) and enoldiazoaceates by dirhodium catalysis.
The intersection of flow cytometry with microfluidics and microfabrication
Authors: Piyasena Menake E. , Graves Steven W.
Published: January 2014

We review microfluidics and microfabrication within flow cytometry and explore synergistic application of microfabrication to modern flow cytometry.
Ullmann-type coupling of brominated tetrathienoanthracene on copper and silver
Authors: Gutzler Rico , Cardenas Luis , Lipton-Duffin Josh , El Garah Mohamed , Dinca Laurentiu E. , Szakacs Csaba E. , Fu Chaoying , Gallagher Mark , Vondráček Martin , Rybachuk Maksym , Perepichka Dmitrii F. , Rosei Federico
Published: January 2014

We present an STM and XPS study on the synthesis of organometallic and covalent polymeric networks and elucidate the role of the substrate on their thermal stability.
Multivalent polymer–Au nanocomposites with cationic surfaces displaying enhanced antimicrobial activity
Authors: Mei Lin , Zhang Xinge , Wang Yanan , Zhang Wei , Lu Zhentan , Luo Yuting , Zhao Yu , Li Chaoxing
Published: January 2014

Pathogenic bacteria pose a catastrophic threat to human health worldwide.
Graphene anchored with ZrO2 nanoparticles as anodes of lithium ion batteries with enhanced electrochemical performance
Authors: Xu Haiping , Yuan Shuai , Wang Zhuyi , Zhao Yin , Fang Jianhui , Shi Liyi
Published: January 2014

Graphene decorated with ZrO2 nanoparticles shows excellent cycle and rate performance as anode material of lithium-ion batteries.
Synthesis and electrocatalytic performance of MnO2-promoted Ag@Pt/MWCNT electrocatalysts for oxygen reduction reaction
Authors: Yu Shuping , Liu Runting , Yang Wensheng , Han Kefei , Wang Zhongming , Zhu Hong
Published: January 2014

A synergic effect between MnO2 and Ag@Pt and the catalyst effect of MnO2 for ORR promote the catalytic efficiency for ORR.
Sulfur-infiltrated three-dimensional graphene-like material with hierarchical pores for highly stable lithium–sulfur batteries
Authors: Li Yunyong , Li Zesheng , Zhang Qinwei , Shen Pei Kang
Published: January 2014

A rational design and synthesis of sulphur–carbon nanocomposites by infiltrating into 3D graphene-like material with hierarchical pores has been achieved for the first time; the nanocomposite shows a highly stable capacity and reversible high charge/discharge rate performance.
Hierarchical structure LiFePO4@C synthesized by oleylamine-mediated method for low temperature applications
Authors: Fan Jingmin , Chen Jiajia , Chen Yongxiang , Huang Haihong , Wei Zhikai , Zheng Ming-sen , Dong Quanfeng
Published: January 2014

A hierarchical nanostructure LiFePO4@C composite was fabricated by an oleylamine mediated method. The as-prepared LiFePO4@C electrode shows superior electrochemical performance, especially at low temperature.
A high conductivity oxide–sulfide composite lithium superionic conductor
Authors: Rangasamy Ezhiylmurugan , Sahu Gayatri , Keum Jong Kahk , Rondinone Adam J. , Dudney Nancy J. , Liang Chengdu
Published: January 2014

A composite of LLZO and LPS inherits the excellent processability of the sulfide and exceeds the conductivity of parent components.
Callyspongisines A–D: bromopyrrole alkaloids from an Australian marine sponge, Callyspongia sp.
Authors: Plisson Fabien , Prasad Pritesh , Xiao Xue , Piggott Andrew M. , Huang Xiao-cong , Khalil Zeinab , Capon Robert J.
Published: January 2014

An Australian Callyspongia sp. yielded the new bromopyrrole alkaloids callyspongisines A–D. Callyspongisine A is only the second reported example of a natural imino-oxazoline and the first to feature a spiro heterocyclic framework.
Global and local exploitation for saliency using bag‐of‐words
Authors: Zheng Zhenzhu , Zhang Yun , Yan Luxin
Published: January 2014

The guidance of attention helps human vision system to detect objects rapidly. In this study, the authors present a new saliency detection algorithm by using bag‐of‐words (BOW) representation. The authors regard salient regions as coming from globally rare features and regions locally differ from their surroundings. Our approach consists of three stages: first, calculate global rarity of visual words. A vocabulary, a group of visual words, is generated from the given image and a rarity factor for each visual word is introduced according to its occurrence. Second, calculate local contrast. Representations of local patch are achieved from the histograms of words. Then, local contrast is computed by the difference between the two BOW histograms of a patch and its surroundings. Finally, saliency is measured by the combination of global rarity and local patch contrast. We compare our model with the previous methods on natural images, and experimental results demonstrate good performance of our model and fair consistency with human eye fixations.
Power conversion interface for small‐capacity wind power generation system
Authors: Wu Jinn‐Chang , Wang Yao‐Hui
Published: January 2014

Power conversion interface for small‐capacity wind power generation system based on permanent‐magnet synchronous generator (PMSG) is proposed in this paper. The proposed power conversion interface will convert the wind power generated from the three‐phase PMSG to a high quality power to inject into the single‐phase utility. This power conversion interface comprises of a power converter and a zero‐sequence transformer set. The power converter is controlled to generate a set of positive‐sequence currents to absorb a real power from the three‐phase PMSG and a set of zero‐sequence currents to pass through the zero‐sequence transformer set to the single‐phase utility. A feed‐forward control is used to control the proposed power conversion interface so as to simplify the control circuit. A simplified maximum power point tracking method is also proposed and incorporated in the control circuit of the power conversion interface to extract the maximum power of the PMSG‐based wind power generation system. Hence, the proposed power conversion interface has the advantages of simplifying both the power circuit and the control circuit. A prototype is developed to demonstrate the performance of the proposed power conversion interface. The experimental results show that the proposed power conversion interface can achieve the expected performance.
Estimation of novel position for the current and potential probe for the fall of potential method
Authors: Nassereddine Mohamad , Rizk Jamal , Hellany Ali , Nagrial Mahmood
Published: January 2014

Earthing system is one of the main key elements in high‐voltage safety management. It presents a safe working environment for workers and people passing by during a fault or malfunction of a power system. Commissioning the earth grid is a critical phase prior to the energizing of the high‐voltage plant. Fall of potential method is commonly used to measure the earth grid resistance of the high‐voltage infrastructure especially high‐voltage transmission pole earth grid. The positions of the current and potential probe play a significant role that leads to precise results. This study endeavours to provide information in regards to the ‘Fall of Potential’ method. It includes the minimum separation required between the current probe and the tested grid. Furthermore, the novel location of the potential probe when the minimum separation between the current and electrode under test cannot be established is analysed. The case study results show the advanced accuracy in the tested result when deploying the novel method as provided in this study. The case study proves the advance accuracy of the proposed novel method especially when the testing area does not permit for a large separation between the tested grid and the current probe.
Synthesising periodic triggering signals with genetic oscillators
Authors: Lin Chun‐Liang , Chen Po‐Kuei
Published: January 2014

The potential of the clock lies in its role of triggering logic reaction for sequential biological circuits. This research introduces an idea of designing a genetic clock generator by Fourier series based on the genetic oscillators. The authors generalise the design idea using a combination of fundamental sinusoidal signals. Since biochemical reaction of the biological system is extremely slow, however, transition between minimal and maximal levels is instantaneous for an ideal clock signal; it is thus not directly realisable in biological systems. That means it would be hard to directly synthesize a square wave generator for use as a genetic clock. They apply Fourier series to represent a square wave as a finite summation of sinusoidal waves generated by some genetic oscillators with different harmonic oscillating frequencies, in which the amplitude alternates at a constant frequency between the fixed minimal and maximal levels with the same duration of time.
Bubble defect control in low‐cost roll‐to‐roll ultraviolet imprint lithography
Authors: Ye Huichun , Shen Lianguan , Li Mujun , Zhang Qiong
Published: January 2014

To obtain high quality patterns in ultraviolet roll‐to‐roll (R2R) imprinting lithography in the atmospheric environment with industrial resins, air bubble defects and the resulting distortion should be avoided in the process. In this reported work, the formation mechanism of the bubble defects is studied systematically with experiments and numerical analysis. The results show that the unsuitable resin coating method mainly contributes to the bubble defects in resin. On the basis of the above conclusions, an improved coating method is proposed in order to reduce the bubbles in the R2R process. This improvement can be applied to the replication of high quality patterns in R2R imprinting with low‐cost industrial resins.
A dynamic slip boundary condition for wall-modeled large-eddy simulation
Authors: Bose S. T. , Moin P.
Published: January 2014

Wall models for large-eddy simulation (LES) are a necessity to remove the prohibitive resolution requirements of near-wall turbulence in high Reynolds turbulent flows. Traditional wall models often rely on assumptions about the local state of the boundary layer (e.g., logarithmic velocity profiles) and require a priori prescription of tunable model coefficients. In the present study, a slip velocity boundary condition for the filtered velocity field is obtained from the derivation of the LES equations using a differential filter. A dynamic procedure for the local slip length is additionally formulated making the slip velocity wall model free of any a priori specified coefficients. The accuracy of the dynamic slip velocity wall model is tested in a series of turbulent channel flows at varying Reynolds numbers and in the LES of a National Advisory Committee for Aeronautics (NACA) 4412 airfoil at near-stall conditions. The wall-modeled simulations are able to accurately predict mean flow characteristics, including the formation of a trailing-edge separation bubble in NACA 4412 configuration. The validation cases demonstrate the effectiveness of this wall-modeling approach in both attached and separated flow regimes.
Cross-stream diffusion in bedload transport
Authors: Seizilles Grégoire , Lajeunesse Eric , Devauchelle Olivier , Bak Michael
Published: January 2014

We investigate experimentally the statistical properties of bedload transport induced by a steady, uniform, and laminar flow. We focus chiefly on lateral transport. The analysis is restricted to experiments where the flow-induced shear stress is just above the threshold for sediment transport. We find that, in this regime, the concentration of moving particles is low enough to neglect interactions between themselves. We can therefore represent bedload as a thin layer of independent walkers travelling over the bed surface. In addition to their downstream motion, the particles show significant fluctuations of their cross-stream velocity, likely due to the roughness of the underlying sediment bed. This causes particles to disperse laterally. Based on thousands of individual trajectories, we show that this lateral spreading is the manifestation of a random walk. The experiments are entirely consistent with Fickian diffusion.
Direct numerical simulation of turbulent mixing at very low Schmidt number with a uniform mean gradient
Authors: Yeung P. K. , Sreenivasan K. R.
Published: January 2014

In a recent direct numerical simulation (DNS) study [P. K. Yeung and K. R. Sreenivasan, “Spectrum of passive scalars of high molecular diffusivity in turbulent mixing,” J. Fluid Mech. 716, R14 (2013)] with Schmidt number as low as 1/2048, we verified the essential physical content of the theory of Batchelor, Howells, and Townsend [“Small-scale variation of convected quantities like temperature in turbulent fluid. 2. The case of large conductivity,” J. Fluid Mech. 5, 134 (1959)] for turbulent passive scalar fields with very strong diffusivity, decaying in the absence of any production mechanism. In particular, we confirmed the existence of the −17/3 power of the scalar spectral density in the so-called inertial-diffusive range. In the present paper, we consider the DNS of the same problem, but in the presence of a uniform mean gradient, which leads to the production of scalar fluctuations at (primarily) the large scales. For the parameters of the simulations, the presence of the mean gradient alters the physics of mixing fundamentally at low Peclet numbers. While the spectrum still follows a −17/3 power law in the inertial-diffusive range, the pre-factor is non-universal and depends on the magnitude of the mean scalar gradient. Spectral transfer is greatly reduced in comparison with those for moderately and weakly diffusive scalars, leading to several distinctive features such as the absence of dissipative anomaly and a new balance of terms in the spectral transfer equation for the scalar variance, differing from the case of zero gradient. We use the DNS results to present an alternative explanation for the observed scaling behavior, and discuss a few spectral characteristics in detail.
Evolution of Griffith's phase in La0.4Bi0.6Mn1−xTixO3 perovskite oxide
Authors: Dayal Vijaylakshmi , Kumar V. Punith , Hadimani R. L. , Jiles D. C.
Published: January 2014

Samples of La0.4Bi0.6Mn1−xTixO3 have been prepared and their microstructure, composition, and magnetic properties have been investigated for x = 0.05, 0.1, and 0.5.The deviation in the inverse susceptibility behavior from Curie-Weiss law and increase in susceptibility exponent indicates the evolution of the Griffith's phase in La0.4Bi0.6Mn1−xTixO3 around TC. The presence of Griffith's Phase is inferred due to magnetic frustration with increasing Ti concentration. The deviation between field cooled and zero field cooled magnetization curves is observed in these samples and is attributed to the appearance of the spin glass or cluster glass state that arises due to the magnetic anisotropy.
Effect of the dynamic pressure on the shock wave structure in a rarefied polyatomic gas
Authors: Taniguchi Shigeru , Arima Takashi , Ruggeri Tommaso , Sugiyama Masaru
Published: January 2014

We study the shock wave structure in a rarefied polyatomic gas based on a simplified model of extended thermodynamics in which the dissipation is due only to the dynamic pressure. In this case the differential system is very simple because it is a variant of Euler system with a new scalar equation for the dynamic pressure [T. Arima, S. Taniguchi, T. Ruggeri, and M. Sugiyama, Phys. Lett. A 376, 2799–2803 (2012)]. It is shown that this theory is able to describe the three types of the shock wave structure observed in experiments: the nearly symmetric shock wave structure (Type A, small Mach number), the asymmetric structure (Type B, moderate Mach number), and the structure composed of thin and thick layers (Type C, large Mach number).
Attracting fixed points for heavy particles in the vicinity of a vortex pair
Authors: Ravichandran S. , Perlekar Prasad , Govindarajan Rama
Published: January 2014

We study the behavior of heavy inertial particles in the flow field of two like-signed vortices. In a frame co-rotating with the two vortices, we find that stable fixed points exist for these heavy inertial particles; these stable frame-fixed points exist only for particle Stokes number St < Stcr. We estimate Stcr and compare this with direct numerical simulations, and find that the addition of viscosity increases the Stcr slightly. We find that the rate at which particles fall into the fixed points increases until the fixed points disappear at St = Stcr. These frame-fixed points are between fixed points and limit cycles in character.
Synthetic genetic array screen identifies PP2A as a therapeutic target in Mad2-overexpressing tumors
Authors: Bian Yang , Kitagawa Risa , Bansal Parmil K. , Fujii Yo , Stepanov Alexander , Kitagawa Katsumi
Published: January 2014

Significance

The spindle checkpoint is required for proper chromosome segregation. Mitotic arrest deficiency 2 (Mad2), a component of the spindle checkpoint, is overexpressed in many cancer cells. This phenotype can be used to specifically kill Mad2-overexpressing tumor cells. Because the spindle checkpoint pathway is highly conserved between yeast and humans, we performed a screen to identify mutants in which Mad2 overexpression kills yeast cells. The screen revealed that Mad2 overexpression induced lethality in 13 gene deletions. Among the human homologs of the 13 candidate genes, a gene encoding protein phosphatase 2 (PP2A) significantly inhibited the growth of Mad2-overexpressing tumor cells. These results indicate that PP2A can be a specific therapeutic target in Mad2-overexpressing tumors.
Private link between signal and response in
Bacillus subtilis
quorum sensing
Authors: Oslizlo Anna , Stefanic Polonca , Dogsa Iztok , Mandic-Mulec Ines
Published: January 2014

Significance

In a social process called “quorum sensing” (QS) bacteria secrete and share signaling molecules that bind to specific receptors and induce adaptive responses within the population. We use the ComQXP QS system of
Bacillus subtilis
to study the intracellular codependence of two essential QS functions: signal production and signal response. We demonstrate that the QS signal-deficient mutants have an overly responsive QS system, a disturbed balance between primary and secondary metabolism, and an overproduction of the secondary metabolite surfactin in the presence of exogenously provided signal. Such mutants fail to compete with the socially active signal producers due to surfactin-related mechanisms that discriminate the two populations. We believe that a constraint on signal production preserves QS functionality in the natural microbial populations.
Normalising breastfeeding
Authors: Mohamad Emma
Published: January 2014

This paper argues that the media can play a role to help normalise breastfeeding in society, particularly in Malaysia. This deduction is reached following an analysis of local media portrayals of breastfeeding, particularly by observing where and how breastfeeding is being portrayed, as well as delving into the division of space between breastfeeding and formula feeding. In addition to the media analysis, the study also looks into several media production issues by interviewing a parenting magazine editor. Findings suggest that local media plays an important role to reinforce breastfeeding as a private activity and subtly divide public/private space through the way producers locate breastfeeding stories and images. The study suggests that in order to normalise breastfeeding, the media should make an effort to portray local women in breastfeeding images and highlight these images in general media outlets.
Utilising information and communication technologies (ICT) for development
Authors: Salman Ali , Abdullah Mohd Yusof Hj. , Aziz Jamaluddin , Ahmad Abdul Latiff , Peng Kee Chang
Published: January 2014

Research in ICT has contributed significantly to the needs of the country in terms of policy formulation, programme implementation and hence the volume of investments in the sector. When Malaysia embarked on ICT as a tool for development of the country with the introduction of the Internet in 1987 by the Malaysian Institute of Microelectronic Systems (MIMOS) through its Rangkaian Komputer Malaysia (RangKom) project, research on the impact of ICT was encouraged and done aggressively. Studies on the impact of ICT have helped in identifying factors that may influence the adoption of ICT and the resulting benefits to the society. This paper discusses the factors that affect the acceptance of ICT among users. The discussion is based on the findings from a quantitative study conducted on 300 internet users. This study gauges the users’ opinion on what motivates them to use ICT and the perceived usefulness of ICT usage. From the findings, ‘perceived usefulness’ and ‘personal factors’ are the main motivating factors in accepting and using ICT. Thus, it encouraged them to use ICT positively in their daily lives as the findings revealed. The findings are crucial for the country in shaping future ICT policies, strategising steps in improving ICT implementation, and in revealing the challenges that need to be addressed. It also enriches the literature on technology acceptance by way of extending the Technology Acceptance Model to include other factors responsible for technology acceptance.
Understanding visual metaphor
Authors: Shahizan Ali Mohd. Nor , Abd. Rahman Mat Pauzi , Salman Ali , Mohammad Salleh Mohd. Azul , Hashim Hasrul
Published: January 2014

Using a history documentary ‘The Kinta Story (1949)’, this article explores the ‘grammar’ of visual metaphor. Numerous images can be found in history documentary, while many more are being planned, which can be accessed by people all around the world. These images technically represent producers’ ideas. They construct connotation and meaning for audiences to read as what the readers want. The visuals are highly posed and set in descript locations to make them usable across the globe. They represent actual places or tragedies and they document witness, which symbolically represents moods such as ‘contentment’ and ‘freedom’. It is argued that visual metaphors cannot be described adequately in formal terms only. Rather, they must be considered as visual representations of metaphorical thoughts or concepts and the changing of time and mass. A cognitive definition of metaphor must not, however, distract from potential variations in meaning and impact which arise from the mode of communication through which metaphors are expressed. This study suggests that many of the dissimilarities between verbal metaphor and its visual counterpart are results from the differences regarding what the two modes are able to express easily and efficiently.
Social-interactional approaches to SLA
Authors: Pekarek Doehler Simona
Published: January 2014

In this paper I address the current state of the art in social-interactional research on SLA. I first provide a brief outline of the historical development of those lines of research that are commonly subsumed under the (broad) heading of ‘social-interactional approaches’, and I discuss their conceptual underpinnings as well as some of their research results. I then focus specifically on current research in what has become a major driving force in socially oriented research on SLA, namely conversation analysis (CA-SLA). I discuss some of the empirical evidence CA-SLA has offered for L2 learning as a socio-cognitive process bound up with the moment-to-moment unfolding of L2 speakers’ social practices. I also review its contribution to our understanding of L2 interactional competence and its development over time. I conclude by sketching avenues for future research.
La liaison en français langue seconde
Authors: Howard Martin
Published: January 2014

This paper presents a longitudinal analysis of French liaison among Irish university learners. Quantitative analysis of their spoken language points to the clear distinction that underlies their use of liaison between obligatory and variable contexts. In the former case, they evidence near-categorical levels of use, while their use of liaison in variable contexts is more frequent than that observed in studies of native speakers in the same age group. Morphosyntactic and lexical analyses indicate that the learners use variable liaison in a small number of morphosyntactic contexts as opposed to the full range within which it is possible, while applying it to a limited number of words within these contexts. The findings are discussed in relation to a number of hypotheses that they raise concerning the acquisition of liaison in L2 French, along with some methodological issues that they evidence concerning the study of liaison in learner language.
A contrastive analysis of the present progressive in French and English
Authors: De Wit Astrid , Patard Adeline , Brisard Frank
Published: January 2014

In this study, we address the semantics of the present progressive constructions in French and English by looking into their present-day uses and their diachronic evolution. Corpus data show that both constructions are frequently used in contemporary English and French to stress the atypical nature of situations. This suggests that these constructions share an epistemic core meaning, which we define as “contingency in immediate reality”. However, in terms of concrete usage types which elaborate this meaning in context, the two progressive constructions differ significantly: the French progressive occurs in fewer types of context than its English counterpart and it is, overall, less frequently used and not obligatory for referring to present-time events, as is usually the case in English. We argue that these differences can be systematically related to the different diachronic evolutions that have shaped the present-tense paradigms in both languages.
INCA: a computational platform for isotopically non-stationary metabolic flux analysis
Authors: Young Jamey D.
Published: January 2014

Summary:  13C flux analysis studies have become an essential component of metabolic engineering research. The scope of these studies has gradually expanded to include both isotopically steady-state and transient labeling experiments, the latter of which are uniquely applicable to photosynthetic organisms and slow-to-label mammalian cell cultures. Isotopomer network compartmental analysis (INCA) is the first publicly available software package that can perform both steady-state metabolic flux analysis and isotopically non-stationary metabolic flux analysis. The software provides a framework for comprehensive analysis of metabolic networks using mass balances and elementary metabolite unit balances. The generation of balance equations and their computational solution is completely automated and can be performed on networks of arbitrary complexity.

Availability and implementation: MATLAB p-code files are freely available for non-commercial use and can be downloaded at http://mfa.vueinnovations.com. Commercial licenses are also available.

Contact:  j.d.young@vanderbilt.edu
Structural integrity of the PCI domain of eIF3a/TIF32 is required for mRNA recruitment to the 43S pre-initiation complexes
Authors: Khoshnevis Sohail , Gunišová Stanislava , Vlčková Vladislava , Kouba Tomáš , Neumann Piotr , Beznosková Petra , Ficner Ralf , Valášek Leoš Shivaya
Published: January 2014

Transfer of genetic information from genes into proteins is mediated by messenger RNA (mRNA) that must be first recruited to ribosomal pre-initiation complexes (PICs) by a mechanism that is still poorly understood. Recent studies showed that besides eIF4F and poly(A)-binding protein, eIF3 also plays a critical role in this process, yet the molecular mechanism of its action is unknown. We showed previously that the PCI domain of the eIF3c/NIP1 subunit of yeast eIF3 is involved in RNA binding. To assess the role of the second PCI domain of eIF3 present in eIF3a/TIF32, we performed its mutational analysis and identified a 10-Ala-substitution (Box37) that severely reduces amounts of model mRNA in the 43–48S PICs in vivo as the major, if not the only, detectable defect. Crystal structure analysis of the a/TIF32-PCI domain at 2.65-Å resolution showed that it is required for integrity of the eIF3 core and, similarly to the c/NIP1-PCI, is capable of RNA binding. The putative RNA-binding surface defined by positively charged areas contains two Box37 residues, R363 and K364. Their substitutions with alanines severely impair the mRNA recruitment step in vivo suggesting that a/TIF32-PCI represents one of the key domains ensuring stable and efficient mRNA delivery to the PICs.
Cellular localization and dynamics of the Mrr type IV restriction endonuclease of Escherichia coli
Authors: Ghosh Anirban , Passaris Ioannis , Tesfazgi Mebrhatu Mehari , Rocha Susana , Vanoirbeek Kristof , Hofkens Johan , Aertsen Abram
Published: January 2014

In this study, we examined the intracellular whereabouts of Mrr, a cryptic type IV restriction endonuclease of Escherichia coli K12, in response to different conditions. In absence of stimuli triggering its activity, Mrr was found to be strongly associated with the nucleoid as a number of discrete foci, suggesting the presence of Mrr hotspots on the chromosome. Previously established elicitors of Mrr activity, such as exposure to high (hydrostatic) pressure (HP) or expression of the HhaII methyltransferase, both caused nucleoid condensation and an unexpected coalescence of Mrr foci. However, although the resulting Mrr/nucleoid complex was stable when triggered with HhaII, it tended to be only short-lived when elicited with HP. Moreover, HP-mediated activation of Mrr typically led to cellular blebbing, suggesting a link between chromosome and cellular integrity. Interestingly, Mrr variants could be isolated that were specifically compromised in either HhaII- or HP-dependent activation, underscoring a mechanistic difference in the way both triggers activate Mrr. In general, our results reveal that Mrr can take part in complex spatial distributions on the nucleoid and can be engaged in distinct modes of activity.
Base excision repair of oxidative DNA damage coupled with removal of a CAG repeat hairpin attenuates trinucleotide repeat expansion
Authors: Xu Meng , Lai Yanhao , Torner Justin , Zhang Yanbin , Zhang Zunzhen , Liu Yuan
Published: January 2014

Trinucleotide repeat (TNR) expansion is responsible for numerous human neurodegenerative diseases. However, the underlying mechanisms remain unclear. Recent studies have shown that DNA base excision repair (BER) can mediate TNR expansion and deletion by removing base lesions in different locations of a TNR tract, indicating that BER can promote or prevent TNR expansion in a damage location–dependent manner. In this study, we provide the first evidence that the repair of a DNA base lesion located in the loop region of a CAG repeat hairpin can remove the hairpin, attenuating repeat expansion. We found that an 8-oxoguanine located in the loop region of CAG hairpins of varying sizes was removed by OGG1 leaving an abasic site that was subsequently 5′-incised by AP endonuclease 1, introducing a single-strand breakage in the hairpin loop. This converted the hairpin into a double-flap intermediate with a 5′- and 3′-flap that was cleaved by flap endonuclease 1 and a 3′-5′ endonuclease Mus81/Eme1, resulting in complete or partial removal of the CAG hairpin. This further resulted in prevention and attenuation of repeat expansion. Our results demonstrate that TNR expansion can be prevented via BER in hairpin loops that is coupled with the removal of TNR hairpins.
PIP degron proteins, substrates of CRL4Cdt2, and not PIP boxes, interfere with DNA polymerase η and κ focus formation on UV damage
Authors: Tsanov Nikolay , Kermi Chames , Coulombe Philippe , Van der Laan Siem , Hodroj Dana , Maiorano Domenico
Published: January 2014

Proliferating cell nuclear antigen (PCNA) is a well-known scaffold for many DNA replication and repair proteins, but how the switch between partners is regulated is currently unclear. Interaction with PCNA occurs via a domain known as a PCNA-Interacting Protein motif (PIP box). More recently, an additional specialized PIP box has been described, the « PIP degron », that targets PCNA-interacting proteins for proteasomal degradation via the E3 ubiquitin ligase CRL4Cdt2. Here we provide evidence that CRL4Cdt2-dependent degradation of PIP degron proteins plays a role in the switch of PCNA partners during the DNA damage response by facilitating accumulation of translesion synthesis DNA polymerases into nuclear foci. We show that expression of a nondegradable PIP degron (Cdt1) impairs both Pol η and Pol κ focus formation on ultraviolet irradiation and reduces cell viability, while canonical PIP box-containing proteins have no effect. Furthermore, we identify PIP degron-containing peptides from several substrates of CRL4Cdt2 as efficient inhibitors of Pol η foci formation. By site-directed mutagenesis we show that inhibition depends on a conserved threonine residue that confers high affinity for PCNA-binding. Altogether these findings reveal an important regulative role for the CRL4Cdt2 pathway in the switch of PCNA partners on DNA damage.
The Next Hundred Years
Authors: Fulford K.W.M. , Davies Martin , Gipps Richard G.T. , Graham George , Sadler John Z. , Stanghellini Giovanni , Thornton Tim
Published: January 2014

This chapter introduces the edited volume,The Oxford Handbook of Philosophy and Psychiatry. Published in 2013, the centenary of Karl Jaspers'General Psychopathology, the chapter draws lessons from the last hundred years for the coming century. No predictions are made. Instead, five 'conditions for flourishing' are set out: 1) Particular Problems - the importance of focussing on well-defined particular problems rather than general theory building, 2) Product- orientation - remaining always responsibly product oriented in the specific sense that both sides (philosophers and practitioners) put in the work necessary to 'go deep' with each other's fields, 3) Partnership - working in partnerships of one kind or another (ranging from team work through to doubly qualified researchers), 4) Process - constant reflection on process based on peer review but leaving scope for the occasional rogue voice to cut innovatively against the grain, and 5) Q - a condition of a different kind, Q is an empirically derived measure of the balance between in-group cohesion and out-group openness required to support creativity. Illustrations are given of how these five conditions for flourishing have underpinned the rapid expansion of philosophy and psychiatry in the closing decades of the twentieth century, and, correspondingly, are also reflected in the Handbook as a whole. Overviews and commentaries on individual contributions to the Handbook are given in extended editorial introductions to each of its eight sections.
Introduction
Authors: Fulford K.W.M. , Davies Martin , Gipps Richard G.T. , Graham George , Sadler John Z. , Stanghellini Giovanni , Thornton Tim
Published: January 2014

In the editorial introduction the stage is set for the chapters in the section by a brief discussion of the relationship between the disciplines of philosophy and psychiatry. Then each chapter briefly is summarized or highlighted.
The Insanity Defense as a History of Mental Disorder
Authors: Robinson Daniel N.
Published: January 2014

Throughout its history, the insanity defense specifically and the more general concept of mental defect or incompetence have been grounded in the assumption that those people fit for the rule of law are able to give and to comprehend reasons for their actions. This chapter traces the evolution of perspectives on the nature of mental illness and the manner in which cultural and extra-scientific influences have shaped perspectives. These perspectives are most saliently expressed in statutory provisions and relevant case law summarized here and covering historical developments from ancient Greece and Rome to the present. Significant interactions between law and psychiatry are further highlighted and informed by core and controversial philosophical assumptions. Attention is given to differences between juridical and medical conceptions of responsibility.
Wilhelm Griesinger
Authors: Arens Katherine
Published: January 2014

This chapter outlines Wilhelm Griesinger's model of the etiology, symptomology, and treatment of mental diseases as a politically activist and scientifically empiricist reading of German Idealist traditions, combining the therapeutics of modern medical practice (including pathology, neurology, anatomy, and medical chemistry) with the kind of Left Hegelian demands on praxis that will emerge in Marx's work. Griesinger (1817-1868) is remembered today as an innovator in medicine and psychiatry who pointed the way for modern-day psychiatric clinical practice, to advances in neuropathology, and to modern strategies for the diagnostics and treatment of mental diseases. Yet his ground-breaking textbookMental Pathology and Therapeuticswas heavily influenced by idealist philosophy in the traditions of Johann Friedrich Herbart and Georg W. F. Hegel. Griesinger situates his own work at the juncture between and clinical or medical psychology and university psychology, what his translators refer to as "medico-metaphysics," a scientific metaphysics of the mind. His project documents a reception of German Idealism stressing nurture, social transformation, and somatic knowledge rather than cognitivism, and provides evidence for a scientific paradigm accommodating induction from material evidence as well as deduction from premises.
From Madness to Mental Illness
Authors: Leoni Federico
Published: January 2014

This chapter explores Michel Foucault's contribution to a critical assessment of modern and contemporary psychiatric practice. It focuses firstly on theHistory of Madness(1961): the social, political, cultural, epistemological construction of the object "psychiatric patient" and "psychiatric pathology"; the gradual historical shift from "madness" to "psychiatric pathology" and its social and epistemological consequences; the horizons and limits of the romantic task Foucault assumes on this basis (namely, the idea of letting the voice of madness come back and speak again, "under" the language and categories of medical knowledge); the critique Jacques Derrida formulated (Writing and Difference, 1967) about this project, and particularly about Foucault's reading of Descartes. Secondly, it examines Foucault's course onPsychiatric Power(1975), focusing on the sociopolitical consequences of this medicalization process: i.e., the construction of the object "psychiatric patient" as "disciplinated bodies", and the general context of this anthropological metamorphosis Foucault studied in his booksDiscipline and Punish,The Will to Knowledge, and in his courseNaissance de la biopolitique(namely, the shift, during the last two centuries, from a disciplinary model to a biopolitical model of power and, more specifically, of administration of mental illness and mental health).
Introduction
Authors: Fulford K.W.M. , Davies Martin , Gipps Richard G.T. , Graham George , Sadler John Z. , Stanghellini Giovanni , Thornton Tim
Published: January 2014

In this introduction to the Section II, the thrust of the component chapters is described. An important strand in the philosophy of psychiatry since its beginnings has been sociopolitical critiques: criticism which aims to improve and humanize psychiatric practice and mental health systems. From this standpoint, the introduction provides an overview of this tradition, including considerations of "postpsychiatry," value commitments in psychiatry, the recovery movement, racism and sexism in the field, and technology.
Introduction
Authors: Fulford K.W.M. , Davies Martin , Gipps Richard G.T. , Graham George , Sadler John Z. , Stanghellini Giovanni , Thornton Tim
Published: January 2014

A cross-disciplinary discussion of the basis of interpersonal relating is of interest to philosophers and psychiatrists for several reasons. The development of successful clinical practice may depend, at least partly, on having an accurate understanding of the basic character of unimpaired interpersonal relating because such understanding can shed light on the nature and source of its disturbed forms. How we think about the basis of "mind-minding" competencies influences how we think about the prognosis and possible treatment of dysfunctional interpersonal relating. Another reason is that philosophical frameworks influence the way we think about and evaluate possible psychiatric disorders and philosophical discussions may be of direct practical importance to psychiatry given that different theories suggest different potential ways of devising therapies.
Varieties of Self-Awareness
Authors: Grünbaum Thor , Zahavi Dan
Published: January 2014

This chapter argues that explicit (reflective) self-conscious thinking is founded on an implicit (pre-reflective) form of self-awareness built into the very structure of phenomenal consciousness. In broad strokes, the argument is that a theory denying the existence of pre-reflective or minimal self-awareness has difficulties explaining a number of essential features of explicit first-person self-reference, and that this will impede a proper understanding of certain types of psychopathology. The chapter proceeds by discussion of a number of prominent theories of self-knowledge and self-reference relating them to forms of self-consciousness. It is then argued that getting these various relations right is important to a proper understanding of a number of psychopathological phenomena.
Empathic Foundations of Clinical Knowledge
Authors: Nyquist Potter Nancy
Published: January 2014

This chapter sets out several views of empathy that draw not only on psychology's literature but on philosophical and psychiatric writings. Empathy is a set of complex concepts involving perception, emotion, attitudinal orientation, and other cognitive processes as well as an activity that expresses character traits and, hence, one of the virtues. In other words, an examination of the philosophical and clinical literature reveals empathy to be not one unified concept but instead a set of related characteristics and qualities needed to be an ethical and therapeutically effective clinician. To this end, the chapter offers reasons as to why empathy is important to clinical work: empathy is both epistemically and ethically necessary to good social relations and, in particular, clinical relations. It then distinguishes empathy from a related concept called "world"-traveling and situates its relevance to therapeutic relations. Finally it brings these ideas together by highlighting Iris Murdoch's ideas of "just vision" and "loving attention."
Discourse and Diseases of the Psyche
Authors: Gillett Grant , Harré Rom
Published: January 2014

The discursive approach to psychiatry, taking as it does an ethological approach to the human organism, directs us to rules and story lines that structure our ways of dealing with the challenges thrown up by particular situated positions in our discursive world. For human beings this means engaging with the sense they are making of the world and the words they use to try and communicate that (to themselves and others). Doing things with words is behavior that draws on certain skills attuned to prompts, cues, expectations, and so on, all of which can go seriously awry in any setting where certain features are unfamiliar or where one of the participants is "impaired" or out of step with prevailing norms and assumptions. Discursive competence and the reality of the human psyche as a mode of being-in-relation-with others crucially depends on intact neural function and brain pathways slowly and cumulatively developed throughout life and is vulnerable to disruption of that substrate. Hysteria (or conversion disorder) and dementia represent two very different situations in which the discursive mismatch between an individual and his or her context of being causes the voice (and soul) of a person to be "lost in translation" so that understanding what is happening and then care and restoration demand a great deal of us not just as biomedical scientists but also as human beings who are reaching out to those who suffer and try to endure (patients) so as to help hold them in being.
Introduction
Authors: Fulford K.W.M. , Davies Martin , Gipps Richard G.T. , Graham George , Sadler John Z. , Stanghellini Giovanni , Thornton Tim
Published: January 2014

The editorial introduction sets the stage for the chapter by identifying the roles that concepts and categories play not just in the field of mental health medicine but in the human mind itself. Then, each chapter is summarized or highlighted.
Ordering Disorder
Authors: Graham George
Published: January 2014

The basic claims of the chapter are, first, that mental disorders are not best understood as types of brain disorder, even though mental disorders are based in the brain. And, second, that the difference between the two sorts of disorders can be illuminated by the sorts of treatment or therapy that may work for the one type (a mental disorder) but not for the other type (a brain disorder). In the discussion some of the diagnostic implications and difficulties associated with these two basic claims are outlined.
The Phenomenology of Affectivity
Authors: Fuchs Thomas
Published: January 2014

In contrast to current opinion which locates mental states including moods and emotions within our head, phenomenology regards affects as encompassing phenomena that connect body, self, and world. Based on the phenomenological approach, the chapter gives a detailed account of: (a) the feeling of being alive or vitality, (b) existential feelings, (c) affective atmospheres, (d) moods, and (e) emotions, emphasizing the embodied as well as intersubjective dimensions of affectivity. Thus, emotions are regarded as resulting from the circular interaction between affective affordances in the environment and the subject's bodily resonance, be it in the form of sensations, postures, gestures, or movement tendencies. A special section deals with the phenomena of interaffectivity, understood as the mutual empathic coupling of two embodied subjects. Psychopathological examples complete the phenomenological account of affectivity.
Introduction
Authors: Fulford K.W.M. , Davies Martin , Gipps Richard G.T. , Graham George , Sadler John Z. , Stanghellini Giovanni , Thornton Tim
Published: January 2014

In this introduction to Section VI, the thrust of the component chapters is described. The classification and diagnosis of mental disorders collects a number of philosophical challenges to the field that call for responses from a variety of philosophical resources: hermeneutics, phenomenology, philosophy of mind, narrative theory, philosophy of science, epistemology-to name a few. The authors in this section address the general challenges in the classification of psychopathology, as well as address particular kinds of mental disorders, including autism, dementia, mania, psychotic disorders, and personality disorders.
Mapping the Domain of Mental Illness
Authors: Poland Jeffrey , Von Eckardt Barbara
Published: January 2014

We argue that dominant research approaches concerning mental illness, which are centered on traditional categories of psychiatric classification as codified in the DSM-IV, have serious empirical, conceptual, and foundational problems. These problems have led to a classification scheme and body of research findings that provide a very poor map of the domain of mental illness, a map that, in turn, undermines clinical and research pursuits. We discuss some current efforts to respond to these problems and argue that the DSM-5 revision process is not very promising, whereas the NIMH Research Domain Criteria initiative and some recent research in cognitive neuroscience fares better, although the latter remains potentially compromised by residual influences of the DSM-based approach. We conclude with some lessons and suggestions for the pursuit of alternative research pathways.