Conformational Dependence of a Protein Kinase Phosphate Transfer Reaction

Atomic motions and energetics for a phosphate transfer reaction catalyzed by the cAMP-dependent protein kinase (PKA) are calculated by plane-wave density functional theory, starting from structures of proteins crystallized in both the reactant conformation (RC) and the transition-state conformation (TC). In the TC, we calculate that the reactants and products are nearly isoenergetic with a 0.2 eV barrier; while phosphate transfer is unfavorable by over 1.2 eV in the RC, with an even higher barrier. With the protein in the TC, the motions involved in reaction are small, with only P$_\gamma$ and the catalytic proton moving more than 0.5 \AA. Examination of the structures reveals that in the RC the active site cleft is not completely closed and there is insufficient space for the phosphorylated serine residue in the product state. Together, these observations imply that the phosphate transfer reaction occurs rapidly and reversibly in a particular conformation of the protein, and that the reaction can be gated by changes of a few tenths of an \AA in the catalytic site.Comment: revtex4, 7 pages, 4 figures, to be submitted to Scienc

Cross-verification of independent quantum devices

Quantum computers are on the brink of surpassing the capabilities of even the most powerful classical computers. This naturally raises the question of how one can trust the results of a quantum computer when they cannot be compared to classical simulation. Here we present a verification technique that exploits the principles of measurement-based quantum computation to link quantum circuits of different input size, depth, and structure. Our approach enables consistency checks of quantum computations within a device, as well as between independent devices. We showcase our protocol by applying it to five state-of-the-art quantum processors, based on four distinct physical architectures: nuclear magnetic resonance, superconducting circuits, trapped ions, and photonics, with up to 6 qubits and 200 distinct circuits

N-[(2-Chloro-3-quinol­yl)meth­yl]-4-fluoro­aniline

In the title compound, C16H12ClFN2, the dihedral angle between the quinoline ring system and the flourophenyl ring is 86.70 (4)°. In the crystal, mol­ecules are linked into chains along the a axis by N—H⋯N hydrogen bonds. In addition, C—H⋯π inter­actions involving the two benzene rings are observed

DBC2, a candidate for a tumor suppressor gene involved in breast cancer

A previously uncharacterized gene, DBC2 (deleted in breast cancer), was cloned from a homozygously deleted region at human chromosome 8p21. DBC2 contains a highly conserved RAS domain and two putative protein interacting domains. Our analyses indicate that DBC2 is the best candidate tumor suppressor gene from this region. It lies within the epicenter of the deletions and is homozygously deleted in 3.5% (7/200) of breast tumors. Mutation analysis of DBC2 led to discovery of two instances of somatic missense mutations in breast tumor specimens, whereas no missense mutations were found in other candidates from the region. Unlike other genes in the region, expression of DBC2 is often extinguished in breast cancer cells or tissues. Moreover, our functional analysis revealed that DBC2 expression in breast cancer cells lacking DBC2 transcripts causes growth inhibition. By contrast, expression of a somatic mutant discovered in a breast cancer specimen does not suppress the growth of breast cancer cells

Poverty and 'Second Economy' in South Africa: An Attempt to Clarify Applicable Concepts and Quantify Extent of Relevant Challenges

In brief, the paper firstly summarises old and new theoretical and technical issues on measuring poverty, secondly analyses poverty from different perspectives and highlights various research findings on poverty trends in South Africa and thirdly clarifies the notion of "second economy" and attempts to "measure" it

Performing the repentant lover in the courtroom: An analysis of Oscar Pistorius’ recreation of hegemonic masculinity

Michel Foucault (1980) presented social theorists with a consideration of power as existing everywhere. Furthermore, Jonathan Heaney (J Polit Power 6:355–362, 2013) recently asserted that emotions and power should be considered conceptual counterparts. I propose that what Foucault referred in terms of the omnipresence of power refers to its deeply social connection to emotions. One emotion, in particular, romantic love, has captured the sociological imagination not only at the level of personal relationships but also in connection with capitalism, as an ideology spurring consumption and influencing the construction of discourses and places. This chapter presents an analysis of the trial of Oscar Pistorius and the analysis plays on two levels: (a) firstly, through his courtroom interactions with members of the defence, and (b) through my eyes as a viewer, witnessing the trial on television. The televised South African courtroom becomes a space for the portrayal of a power-suffused masculine identity, which is emotionally constituted through emotional control and emotional release

Poverty and Well-being in Post-Apartheid South Africa: An Overview of Data, Outcomes and Policy

WP 2006-03 January 2006This is an overview of poverty and well-being in the first decade of post-apartheid South Africa. It is an introduction to a volume that brings together some of the most prominent academic research done on this topic for the 10-year review process in South Africa. This overview highlights three key aspects of the picture that the detailed research paints. First, data quality and comparability has been a constant issue in arriving at a consensus among analysts on the outcomes for households and individuals in postapartheid South Africa. Second, while the outcomes on unemployment, poverty and inequality are indeed bad, the outcomes on social indicators and access to public services are much more encouraging. Third, the prospects for rapid and sustained economic growth, without which poverty and well-being cannot be addressed in the long run, are themselves negatively affected by increasing inequality, poverty and unemployment

Cloud computing and RESERVOIR project

The support for complex services delivery is becoming a key point in current internet technology. Current trends in internet applications are characterized by on demand delivery of ever growing amounts of content. The future internet of services will have to deliver content intensive applications to users with quality of service and security guarantees. This paper describes the RESERVOIR project and the challenge of a reliable and effective delivery of services as utilities in a commercial scenario. It starts by analyzing the needs of a future infrastructure provider and introducing the key concept of a service oriented architecture that combines virtualisation-aware grid with grid-aware virtualisation, while being driven by business service management. This article will then focus on the benefits and the innovations derived from the RESERVOIR approach. Eventually, a high level view of RESERVOIR general architecture is illustrated