Identification of candidate small-molecule therapeutics to cancer by gene-signature perturbation in connectivity mapping.

Connectivity mapping is a recently developed technique for discovering the underlying connections between different biological states based on gene-expression similarities. The sscMap method has been shown to provide enhanced sensitivity in mapping meaningful connections leading to testable biological hypotheses and in identifying drug candidates with particular pharmacological and/or toxicological properties. Challenges remain, however, as to how to prioritise the large number of discovered connections in an unbiased manner such that the success rate of any following-up investigation can be maximised. We introduce a new concept, gene-signature perturbation, which aims to test whether an identified connection is stable enough against systematic minor changes (perturbation) to the gene-signature. We applied the perturbation method to three independent datasets obtained from the GEO database: acute myeloid leukemia (AML), cervical cancer, and breast cancer treated with letrozole. We demonstrate that the perturbation approach helps to identify meaningful biological connections which suggest the most relevant candidate drugs. In the case of AML, we found that the prevalent compounds were retinoic acids and PPAR activators. For cervical cancer, our results suggested that potential drugs are likely to involve the EGFR pathway; and with the breast cancer dataset, we identified candidates that are involved in prostaglandin inhibition. Thus the gene-signature perturbation approach added real values to the whole connectivity mapping process, allowing for increased specificity in the identification of possible therapeutic candidates.

A hypercyclic finite rank perturbation of a unitary operator

A unitary operator V and a rank 2 operator R acting on a Hilbert space H are constructed such that V + R is hypercyclic. This answers affirmatively a question of Salas whether a finite rank perturbation of a hyponormal operator can be supercyclic.

Proton radiography as an electromagnetic field and density perturbation diagnostic (invited)

Laser driven proton beams have been used to diagnose transient fields and density perturbations in laser produced plasmas. Grid deflectometry techniques have been applied to proton radiography to obtain precise measurements of proton beam angles caused by electromagnetic fields in laser produced plasmas. Application of proton radiography to laser driven implosions has demonstrated that density conditions in compressed media can be diagnosed with million electron volt protons. This data has shown that proton radiography can provide unique insight into transient electromagnetic fields in super critical density plasmas and provide a density perturbation diagnostics in compressed matter.

Electronic properties of interfaces and defects from many-body perturbation theory: Recent developments and applications

We review some recent developments in many body perturbation theory (MBPT) calculations that have enabled the study of interfaces and defects. Starting from the theoretical basis of MBPT, Hedin's equations are presented, leading to the CW and CWI' approximations. We introduce the perturbative approach, that is the one most commonly used for obtaining quasiparticle (QP) energies. The practical strategy presented for dealing with the frequency dependence of the self energy operator is based on either plasmon-pole models (PPM) or the contour deformation technique, with the latter being more accurate. We also discuss the extrapolar method for reducing the number of unoccupied states which need to be included explicity in the calculations. The use of the PAW method in the framework of MBPT is also described. Finally, results which have been obtained using, MBPT for band offsets a interfaces and for defects presented, with companies on the main difficulties and cancels.

Schematic representation of the QP corrections (marked with ) to the band edges (E and E-v) and a defect level (F) for a Si/SiO2 interface (Si and O atoms are represented in blue and red, respectively, in the ball and stick model) with an oxygen vacancy leading to a Si-Si bond (the Si atoms involved in this bond are colored light blue).

Electronic properties of zircon and hafnon from many-body perturbation theory

The electronic properties of zircon and hafnon, two wide-gap high-kappa materials, are investigated using many-body perturbation theory (MBPT) combined with the Wannier interpolation technique. For both materials, the calculated band structures differ from those obtained within density-functional theory and MBPT by (i) a slight displacement of the highest valence-band maximum from the Gamma point and (ii) an opening of the indirect band gap to 7.6 and 8.0 eV for zircon and hafnon, respectively. The introduction of vertex corrections in the many-body self-energy does not modify the results except for a global rigid shift of the many-body corrections.

Density functionals from many-body perturbation theory: The band gap for semiconductors and insulators

Theoretically the Kohn-Sham band gap differs from the exact quasiparticle energy gap by the derivative discontinuity of the exchange-correlation functional. In practice for semiconductors and insulators the band gap calculated within any local or semilocal density approximations underestimates severely the experimental energy gap. On the other hand, calculations with an "exact" exchange potential derived from many-body perturbation theory via the optimized effective potential suggest that improving the exchange-correlation potential approximation can yield a reasonable agreement between the Kohn-Sham band gap and the experimental gap. The results in this work show that this is not the case. In fact, we add to the exact exchange the correlation that corresponds to the dynamical (random phase approximation) screening in the GW approximation. This accurate exchange-correlation potential provides band structures similar to the local density approximation with the corresponding derivative discontinuity that contributes 30%-50% to the energy gap. Our self-consistent results confirm substantially the results for Si and other semiconductors obtained perturbatively [R. W. Godby , Phys. Rev. B 36, 6497 (1987)] and extend the conclusion to LiF and Ar, a wide-gap insulator and a noble-gas solid. (c) 2006 American Institute of Physics.

Rethinking the Sacred and Secular Divide. Accounting and Accountability Practices in the Diocese of Ferrara (1431-1457)

Purpose – Informed by the work of Laughlin and Booth, the paper analyses the role of accounting and accountability practices within the 15th century Roman Catholic Church, more specifically within the Diocese of Ferrara (northern Italy), in order to determine the presence of a sacred-secular dichotomy. Pope Eugenius IV had embarked upon a comprehensive reform of the Church to counter the spreading moral corruption within the clergy and the subsequent disaffection with the Church by many believers. The reforms were notable not only for the Pope’s determination to restore the moral authority and power of the Church but for the essential contributions of ‘profane’ financial and accounting practices to the success of the reforms.
Design/methodology/approach – Original 15th century Latin documents and account books of the Diocese of Ferrara are used to highlight the link between the new sacred values imposed by Pope Eugenius IV’s reforms and accounting and accountability practices.
Findings – The documents reveal that secular accounting and accountability practices were not regarded as necessarily antithetical to religious values, as would be expected by Laughlin and Booth. Instead, they were seen to assume a role which was complementary to the Church’s religious mission. Indeed, they were essential to its sacred mission during a period in which the Pope sought to arrest the moral decay of the clergy and reinstate the Church’s authority. Research implications/limitations – The paper shows that the sacred-secular dichotomy cannot be considered as a priori valid in space and time. There is also scope for examining other Italian dioceses where there was little evidence of Pope Eugenius’ reforms.
Originality/value – The paper presents a critique of the sacred-secular divide paradigm by considering an under-researched period and a non Anglo-Saxon context.