Energy and symmetry of dddd excitations in undoped layered cuprates measured by Cu L3L_3 resonant inelastic x-ray scattering

We measured high resolution Cu $L_3$ edge resonant inelastic x-ray scattering (RIXS) of the undoped cuprates La$_2$CuO$_4$, Sr$_2$CuO$_2$Cl$_2$, CaCuO$_2$ and NdBa$_2$Cu$_3$O$_6$. The dominant spectral features were assigned to $dd$ excitations and we extensively studied their polarization and scattering geometry dependence. In a pure ionic picture, we calculated the theoretical cross sections for those excitations and used them to fit the experimental data with excellent agreement. By doing so, we were able to determine the energy and symmetry of Cu-3$d$ states for the four systems with unprecedented accuracy and confidence. The values of the effective parameters could be obtained for the single ion crystal field model but not for a simple two-dimensional cluster model. The firm experimental assessment of $dd$ excitation energies carries important consequences for the physics of high $T_c$ superconductors. On one hand, having found that the minimum energy of orbital excitation is always $\geq 1.4$ eV, i.e., well above the mid-infrared spectral range, leaves to magnetic excitations (up to 300 meV) a major role in Cooper pairing in cuprates. On the other hand, it has become possible to study quantitatively the effective influence of $dd$ excitations on the superconducting gap in cuprates.Comment: 22 pages, 11 figures, 1 tabl

Foreign policy beliefs and support for Stephen Harper and the Conservative Party

Similar to other recent Canadian elections, foreign policy did not feature prominently in the 2011 federal election campaign. In fact, many doubt Canadian public opinion on international affairs is linked to the actions taken by recent Governments. In this paper, we examine Canadian public opinion toward a range of foreign policy issues and argue that the survey questions measure two latent dimensions —militarism and internationalism. Our survey evidence indicates the existence of an “issue public” which is prepared to endorse military action and is skeptical of human rights and overseas aid programs, and this group is far more supportive of Prime Minister Harper and the Conservative Party than other Canadians. The absence of an elite discussion, either among politicians or between media elites, about the direction of Canadian foreign policy does not prevent the Canadian voter from thinking coherently about questions pertaining to this issue domain and employing these beliefs to support or oppose political parties and their leaders

Roadmap on Li-ion battery manufacturing research

Growth in the Li-ion battery market continues to accelerate, driven primarily by the increasing need for economic energy storage for electric vehicles. Electrode manufacture by slurry casting is the first main step in cell production but much of the manufacturing optimisation is based on trial and error, know-how and individual expertise. Advancing manufacturing science that underpins Li-ion battery electrode production is critical to adding to the electrode manufacturing value chain. Overcoming the current barriers in electrode manufacturing requires advances in materials, manufacturing technology, in-line process metrology and data analytics, and can enable improvements in cell performance, quality, safety and process sustainability. In this roadmap we explore the research opportunities to improve each stage of the electrode manufacturing process, from materials synthesis through to electrode calendering. We highlight the role of new process technology, such as dry processing, and advanced electrode design supported through electrode level, physics-based modelling. Progress in data driven models of electrode manufacturing processes is also considered. We conclude there is a growing need for innovations in process metrology to aid fundamental understanding and to enable feedback control, an opportunity for electrode design to reduce trial and error, and an urgent imperative to improve the sustainability of manufacture

Adult Raphe-Specific Deletion of Lmx1b Leads to Central Serotonin Deficiency

The transcription factor Lmx1b is essential for the differentiation and survival of central serotonergic (5-HTergic) neurons during embryonic development. However, the role of Lmx1b in adult 5-HTergic neurons is unknown. We used an inducible Cre-LoxP system to selectively inactivate Lmx1b expression in the raphe nuclei of adult mice. Pet1-CreERT2 mice were generated and crossed with Lmx1bflox/flox mice to obtain Pet1-CreERT2; Lmx1bflox/flox mice (which termed as Lmx1b iCKO). After administration of tamoxifen, the level of 5-HT in the brain of Lmx1b iCKO mice was reduced to 60% of that in control mice, and the expression of tryptophan hydroxylase 2 (Tph2), serotonin transporter (Sert) and vesicular monoamine transporter 2 (Vmat2) was greatly down-regulated. On the other hand, the expression of dopamine and norepinephrine as well as aromatic L-amino acid decarboxylase (Aadc) and Pet1 was unchanged. Our results reveal that Lmx1b is required for the biosynthesis of 5-HT in adult mouse brain, and it may be involved in maintaining normal functions of central 5-HTergic neurons by regulating the expression of Tph2, Sert and Vmat2

AcrB Trimer Stability and Efflux Activity, Insight from Mutagenesis Studies

The multidrug transporter AcrB in Escherichia coli exists and functions as a homo-trimer. The assembly process of obligate membrane protein oligomers, including AcrB, remains poorly understood. In a previous study, we have shown that individual AcrB subunit is capable of folding independently, suggesting that trimerization of AcrB follows a three-stage pathway in which monomers first fold, and then assemble. Here we destabilized the AcrB trimer through mutating a single Pro (P223) in the protruding loop of AcrB, which drastically reduced the protein activity. We replaced P223 separately with five residues, including Ala, Val, Tyr, Asn, and Gly, and found that AcrBP223G was the least active. Detailed characterization of AcrBP223G revealed that the protein existed as a well-folded monomer after purification, but formed a trimer in vivo. The function of the mutant could be partly restored through strengthening the stability of the trimer using an inter-subunit disulfide bond. Our results also suggested that the protruding loop is well structured during AcrB assembly with P223 served as a “wedge” close to the tip to stabilize the AcrB trimer structure. When this wedge is disrupted, the stability of the trimer is reduced, accompanied by a decrease of drug efflux activity

Image rights: Exploitation and legal control in English and Hungarian law

In the past decades due to changed technical advances, features of the personality have become economically exploitable to an extent not previously known. Pop stars, TV celebrities as well as famous athletes have sought protection against the commercial use of their images, names and likenesses without their consent.1 Despite the economic value of personality and image rights, there is currently no international standard or agreed legal concept for recognising an image right. While many jurisdictions, for example, the US, Germany, France and Hungary offer express statutory protection against the unauthorised commercial use of an individual’s image by a third party in the context of publicity or personality rights, English law provides no cause of action for the infringement of image rights as such. Although a celebrity may currently obtain protection through various statutory and common law rights, such as the developing law of privacy, trade mark law breach of confidence and, in particular, the tort of passing off, none of these rights were designed to protect image or personality rights.2 In this context, this article explores the potentially enforceable rights, their benefits and practical strategies to protect name and image rights in the UK3 and Hungary

Roadmap on Li-ion battery manufacturing research

Growth in the Li-ion battery market continues to accelerate, driven by increasing need for economic energy storage in the electric vehicle market. Electrode manufacture is the first main step in production and in an industry dominated by slurry casting, much of the manufacturing process is based on trial and error, know-how and individual expertise. Advancing manufacturing science that underpins Li-ion battery electrode production is critical to adding value to the electrode manufacturing value chain. Overcome the current barriers in the electrode manufacturing requires advances in material innovation, manufacturing technology, in-line process metrology and data analytics to improve cell performance, quality, safety and process sustainability. In this roadmap we present where fundamental research can impact advances in each stage of the electrode manufacturing process from materials synthesis to electrode calendering. We also highlight the role of new process technology such as dry processing and advanced electrode design supported through electrode level, physics-based modelling. To compliment this, the progresses in data driven models of full manufacturing processes is reviewed. For all the processes we describe, there is a growing need process metrology, not only to aid fundamental understanding but also to enable true feedback control of the manufacturing process. It is our hope this roadmap will contribute to this rapidly growing space and provide guidance and inspiration to academia and industry

A short history of the 5-HT2C receptor: from the choroid plexus to depression, obesity and addiction treatment

This paper is a personal account on the discovery and characterization of the 5-HT2C receptor (first known as the 5- HT1C receptor) over 30 years ago and how it translated into a number of unsuspected features for a G protein-coupled receptor (GPCR) and a diversity of clinical applications. The 5-HT2C receptor is one of the most intriguing members of the GPCR superfamily. Initially referred to as 5-HT1CR, the 5-HT2CR was discovered while studying the pharmacological features and the distribution of [3H]mesulergine-labelled sites, primarily in the brain using radioligand binding and slice autoradiography. Mesulergine (SDZ CU-085), was, at the time, best defined as a ligand with serotonergic and dopaminergic properties. Autoradiographic studies showed remarkably strong [3H]mesulergine-labelling to the rat choroid plexus. [3H]mesulergine-labelled sites had pharmacological properties different from, at the time, known or purported 5-HT receptors. In spite of similarities with 5-HT2 binding, the new binding site was called 5-HT1C because of its very high affinity for 5-HT itself. Within the following 10 years, the 5-HT1CR (later named 5- HT2C) was extensively characterised pharmacologically, anatomically and functionally: it was one of the first 5-HT receptors to be sequenced and cloned. The 5-HT2CR is a GPCR, with a very complex gene structure. It constitutes a rarity in theGPCR family: many 5-HT2CR variants exist, especially in humans, due to RNA editing, in addition to a few 5-HT2CR splice variants. Intense research led to therapeutically active 5-HT2C receptor ligands, both antagonists (or inverse agonists) and agonists: keeping in mind that a number of antidepressants and antipsychotics are 5- HT2CR antagonists/inverse agonists. Agomelatine, a 5-HT2CR antagonist is registered for the treatment of major depression. The agonist Lorcaserin is registered for the treatment of aspects of obesity and has further potential in addiction, especially nicotine/ smoking. There is good evidence that the 5-HT2CR is involved in spinal cord injury-induced spasms of the lower limbs, which can be treated with 5-HT2CR antagonists/inverse agonists such as cyproheptadine or SB206553. The 5-HT2CR may play a role in schizophrenia and epilepsy. Vabicaserin, a 5-HT2CR agonist has been in development for the treatment of schizophrenia and obesity, but was stopped. As is common, there is potential for further indications for 5-HT2CR ligands, as suggested by a number of preclinical and/or genome-wide association studies (GWAS) on depression, suicide, sexual dysfunction, addictions and obesity. The 5-HT2CR is clearly affected by a number of established antidepressants/antipsychotics and may be one of the culprits in antipsychotic-induced weight gain