Prioritization of charge over geometry in transition state analogues of a dual specificity protein kinase

The direct observation of a transition state analogue (TSA) complex for tyrosine phosphorylation by a signaling kinase has been achieved using (19)F NMR analysis of MEK6 in complex with tetrafluoroaluminate (AlF(4)(-)), ADP, and p38α MAP kinase (acceptor residue: Tyr182). Solvent-induced isotope shifts and chemical shifts for the AlF(4)(-) moiety indicate that two fluorine atoms are coordinated by the two catalytic magnesium ions of the kinase active site, while the two remaining fluorides are liganded by protein residues only. An equivalent, yet distinct, AlF(4)(-) complex involving the alternative acceptor residue in p38α (Thr180) is only observed when the Tyr182 is mutated to phenylalanine. The formation of octahedral AlF(4)(-) species for both acceptor residues, rather than the trigonal bipyramidal AlF(3)(0) previously identified in the only other metal fluoride complex with a protein kinase, shows the requirement of MEK6 for a TSA that is isoelectronic with the migrating phosphoryl group. This requirement has hitherto only been demonstrated for proteins having a single catalytic magnesium ion.     

Transitioning to the Common Core State Standards for Mathematics: A Mixed Methods Study of Elementary Teachers’ Experiences and Perspectives

This mixed methods study explored elementary teachers’ (n = 73) experiences with and perspectives on the recently implemented Common Core State Standards for Mathematics (CCSS‐Mathematics) at a high‐needs, urban school. Analysis of the survey, questionnaire, and interview data reveals the findings cluster around: familiarity with and preparation to use the standards; implementation of the standards, including incorporation and teacher change; and tensions associated with enactment of the standards. Notably, the teachers believed in the merit of the standards but were constrained by their inadequate content knowledge, limited aligned curricular resources, lack of student readiness, and a perceived mismatch with ELLs. The results illuminate the professional needs of teachers during this critical time of transition to the standards and also add to the scant research on this national‐scale reform in mathematics education. This article features a Research to Practice Companion Article . Please click on the supporting information link below to access.     

Multiaxial constitutive model accounting for the strength-differential in Inconel 718

The nickel-base alloy Inconel 718 exhibits a strength-differential, that is, a different plastic flow behavior in uniaxial tension and uniaxial compression. A phenomenological viscoplastic model founded on thermodynamics has been extended for material behavior that deviates from classical metal plasticity by including all three stress invariants in the threshold function. The model can predict plastic flow in isotropic materials with or without a flow stress asymmetry as well as with or without pressure dependence. Viscoplastic material parameters have been fit to pure shear, uniaxial tension, and uniaxial compression experimental results at 650°°C. Threshold function material parameters have been fit to the strength-differential. Four classes of threshold functions have been considered and nonproportional loading of hollow tubes, such as shear strain followed by axial strain, has been used to select the most applicable class of threshold function for the multiaxial model as applied to Inconel 718 at 650 °C. These nonproportional load paths containing corners provide a rigorous test of a plasticity model, whether it is time-dependent or not. A J₂J₃ class model, where J₂ and J₃ are the second and third effective deviatoric stress invariants, was found to agree the best with the experimental results.     

The fiftieth anniversary of the liquid crystal display

ABSTRACT

A record is given of the special meeting organised by the UK&I Chapter of the Society of Information Display held at the Royal Academy of Engineering in London, to celebrate the 50th anniversary of the RCA announcement of the first Liquid Crystal Display on 28th May 1968. Coming exactly eighty years after the report of the first liquid crystal materials, this announcement sparked interest across the globe, and particularly in the UK, Switzerland and Japan. Presentations of the early LCD history from Hilsum, Schadt and Raynes give insights into both the science and also the process of invention itself. These early contributors are followed by a view from the USA from Bos and representation from the companies Sharp and Merck that helped shape the success of these fascinating and useful materials. Also reviewed are talks on the use of organic semiconductors to drive plastic LCD by Sirringhaus, reflective LCD of Folium Optics, retail signage of Displaydata, as well as a look to the future from LCD competitors from Bodle (Phase Change Material displays) and BOE (OLED).     

People In The News

Abstract

In November 1999 the title of Chevalier dans I'Ordre des Palmes Academiques has been conferred by the French Government on Professor 5. Chandrasekhar, Centre for Liquid Crystal Research, Bangalore, India, in recognition of ‘outstanding work as a Researcher and Professor’. The citation also notes that the award is ‘pour services rendus a la culture Fransaise’.

The Charles Vernon Boys medal and prize has been awarded for the year 2000 to Dr Cliff Jones of the UK Defence Evaluation and Research Agency, Malvern, UK. This award is made annually by the Institute of Physics to young scientists, of not more than 35 years of age, for distinguished research in experimental physics. The award was made to Cliff Jones for outstanding contributions to the development of liquid crystal displays. His research has covered areas including new materials, addressing techniques and panel fabrication. He has made major contributions to the development of ferroelectric liquid crystal displays, and has been closely involved in this area with a major Anglo-Japanese innovation programme with Sharp Corporation. The successful outcome of this programme is a prototype 17 inch FLC flat screen television, which was recently demonstrated in Japan.     

Torsion-Free Space Groups, 2-Cohomology, and Scott Modules

For a subgroupCof orderpof a finite groupG, we find the summandMof thep-adic permutation module ind_C^GZ_psuch thatH²(G, M)≠0, and determine whenMis the Scott module. This is applied to the study of torsion-free space groups.     

A general and rapid cell-free approach for the interrogation of protein-protein, protein-DNA, and protein-RNA interactions and their antagonists utilizing split-protein reporters

Split-protein reporters have emerged as a powerful methodology for imaging biomolecular interactions which are of much interest as targets for chemical intervention. Herein we describe a systematic evaluation of split-proteins, specifically the green fluorescent protein, beta-lactamase, and several luciferases, for their ability to function as reporters in completely cell-free systems to allow for the extremely rapid and sensitive determination of a wide range of biomolecular interactions without the requirement for laborious transfection, cell culture, or protein purification (12-48 h). We demonstrate that the cell-free split-luciferase system in particular is amenable for directly interrogating protein-protein, protein-DNA, and protein-RNA interactions in homogeneous assays with very high sensitivity (22-1800 fold) starting from the corresponding mRNA or DNA. Importantly, we show that the cell-free system allows for the rapid (2 h) identification of target-site specificity for protein-nucleic acid interactions and in evaluating antagonists of protein-protein and protein-peptide complexes circumventing protein purification bottlenecks. Moreover, we show that the cell-free split-protein system is adaptable for analysis of both protein-protein and protein-nucleic acid interactions in artificial cell systems comprising water-in-oil emulsions. Thus, this study provides a general and enabling methodology for the rapid interrogation of a wide variety of biomolecular interactions and their antagonists without the limitations imposed by current in vitro and in vivo approaches.