DNA-dependent Protein Kinase-mediated Phosphorylation of Protein Kinase B Requires a Specific Recognition Sequence in the C-terminal Hydrophobic Motif

DNA-dependent protein kinase (DNA-PK) has been implicated in a variety of nuclear processes including DNA double strand break repair, V(D)J recombination, and transcription. A recent study showed that DNA-PK is responsible for Ser-473 phosphorylation in the hydrophobic motif of protein kinase B (PKB/Akt) in genotoxic-stressed cells, suggesting a novel role for DNA-PK in cell signaling. Here, we report that DNA-PK activity toward PKB peptides is impaired in DNA-PK knock-out mouse embryonic fibroblast cells when compared with wild type. In addition, human glioblastoma cells expressing a mutant form of DNA-PK (M059J) displayed a lower DNA-PK activity when compared with glioblastoma cells expressing wild-type DNA- PK (M059K) when PKB peptide substrates were tested. DNA- PK preferentially phosphorylated PKB on Ser-473 when compared with its known in vitro substrate, p53. A consensus hydrophobic amino acid surrounding the Ser-473 phospho-acceptor site in PKB containing amino acids Phe at position +1 and +4 and Tyr at position -1 are critical for DNA- PK activity. Thus, these data define the specificity of DNA- PK action as a Ser-473 kinase for PKB in DNA repair signaling.

An efficient feature selection method for mobile devices with application to activity recognition

This paper presents a feature selection method for data classification, which combines a model-based variable selection technique and a fast two-stage subset selection algorithm. The relationship between a specified (and complete) set of candidate features and the class label is modelled using a non-linear full regression model which is linear-in-the-parameters. The performance of a sub-model measured by the sum of the squared-errors (SSE) is used to score the informativeness of the subset of features involved in the sub-model. The two-stage subset selection algorithm approaches a solution sub-model with the SSE being locally minimized. The features involved in the solution sub-model are selected as inputs to support vector machines (SVMs) for classification. The memory requirement of this algorithm is independent of the number of training patterns. This property makes this method suitable for applications executed in mobile devices where physical RAM memory is very limited. An application was developed for activity recognition, which implements the proposed feature selection algorithm and an SVM training procedure. Experiments are carried out with the application running on a PDA for human activity recognition using accelerometer data. A comparison with an information gain based feature selection method demonstrates the effectiveness and efficiency of the proposed algorithm.

FPGA Implementation of a Pipelined Gaussian Calculation for HMM-Based Large Vocabulary Speech Recognition

A scalable large vocabulary, speaker independent speech recognition system is being developed using Hidden Markov Models (HMMs) for acoustic modeling and a Weighted Finite State Transducer (WFST) to compile sentence, word, and phoneme models. The system comprises a software backend search and an FPGA-based Gaussian calculation which are covered here. In this paper, we present an efficient pipelined design implemented both as an embedded peripheral and as a scalable, parallel hardware accelerator. Both architectures have been implemented on an Alpha Data XRC-5T1, reconfigurable computer housing a Virtex 5 SX95T FPGA. The core has been tested and is capable of calculating a full set of Gaussian results from 3825 acoustic models in 9.03 ms which coupled with a backend search of 5000 words has provided an accuracy of over 80%. Parallel implementations have been designed with up to 32 cores and have been successfully implemented with a clock frequency of 133?MHz.

Protein surface recognition using geometrically pure Ru(II) tris(bipyridine) derivatives

This manuscript illustrates that the geometric arrangement of protein-binding groups around a ruthenium(II) core leads to dramatic differences in cytochrome c (cyt c) binding highlighting that it is possible to define synthetic receptors with shape complementarity to protein surfaces.

Molecular testing of respiratory swabs aids early recognition of meningococcal disease in children

Early meningococcal disease (MD) diagnosis is difficult. We assessed rapid molecular testing of respiratory specimens. We performed genotyping of respiratory swabs, blood, and cerebrospinal fluid from children with suspected disease and nasal swabs (NSs) from matched controls. Thirty-nine of 104 suspected cases had confirmed disease. Four controls were carriers. Throat swab ctrA and porA testing for detection of disease gave a sensitivity of 81% (17/21), specificity of 100% (44/44), positive predictive value (PPV) of 100% (17/17), negative predictive value (NPV) of 92% (44/48), and relative risk of 12. NS ctrA and porA testing gave a sensitivity of 51% (20/39), specificity of 95% (62/65), PPV of 87% (20/23), NPV of 77% (62/81), and relative risk of 4. Including only the 86 NSs taken within 48 h of presentation, the results were sensitivity of 60% (18/30), specificity of 96% (54/56), PPV of 90% (18/20), NPV of 82% (54/66), and relative risk of 5. Swab type agreement was excellent (kappa 0.80, P

Demanding Recognition: Equality, Respect, and Esteem

This article argues that we must distinguish between two distinct currents in the politics of recognition, one centred on demands for equal respect which is consistent with liberal egalitarianism, and one which centres on demands for esteem made on behalf of particular groups which is at odds with egalitarian aims. A variety of claims associated with the politics of recognition are assessed and it is argued that these are readily accommodated within contemporary liberal egalitarian theory. It is argued that, pace Taylor, much of what passes for `identity' or recognition politics is driven by demands for equal respect, not by demands for esteem/affirmation. Given the inherently hierarchical nature of esteem recognition, no liberal state can consistently grant such recognition. Furthermore, these demands pose the risk of intensifying intergroup competition and chauvinism. Esteem recognition is valuable for individuals, but plays a problematic role for egalitarian politics.

Platinum(II) phosphine and orotate complexes with aminopyridine co-ligands, and their molecular recognition via hydrogen bonding

The new complexes [Pt(dppp)(py)(2)][OTf](2), 1, [Pt(dppp)(2-ap)(2)][OTf](2), 2, [(dppp)Pt(mu -OH){mu -NH(C5H3N)NH2}Pt(dppp)][OTf](2), 3 (py=pyridine, 2-ap=2-aminopyridine, NH(C5H3N)NH2=2,6-diaminopyridine anion, dppp = 1,3-bis(diphenylphosphino)propane, OTf=O3SCF3) have been prepared via reactions between [Pt(dppp)(OTf)(2)] and pyridine, 2-aminopyridine or 2,6-diaminopyridine (2,6-dap) respectively. The amines exhibit a range of co-ordination modes. Pyridine and 2-aminopyridine co-ordinate to platinum through endo-nitrogen atoms in complexes 1 and 2, the latter existing as a pair of rotomers due to the steric hindrance introduced by the 2-substituent. However, 2,6-diaminopyridine co-ordinates to platinum through the exo-nitrogen of one amino group, to give the unusual mu -amido complex 3. Reaction of the known orotate chelate complex [Pt(PEt3)(2)(N,O-HL)] [HL=orotate, the dianion of 2,6-dioxo-1,2,3,6-tetrahydropyrimidine-4-carboxylic acid (orotic acid)] with 2,6-dap gave [Pt(PEt3)(2)(2,6-dap)(N-HL)] 4, which contains an unconventional monodentate orotate ligand. In this co-ordination mode the orotate retains an ADA hydrogen bonding site and was found to co-crystallise with 2,6-dap via complementary ADA:DAD triple hydrogen bonds to give [Pt(PEt3)(2)(N-HL)(2,6-dap)].2,6-dap, 5. Complex 5 exhibits a helical chain structure of associated [1+1] adducts in the solid state.