Problems Affecting Labor

Much experimental work has been devoted in comparing the folding behavior of proteins sharing the same fold but different sequence. The recent design of proteins displaying very high sequence identities but different 3D structure allows the unique opportunity to address the protein-folding problem from a complementary perspective. Here we explored by ℙ-value analysis the pathways of folding of three different heteromorphic pairs, displaying increasingly high-sequence identity (namely, 30%, 77%, and 88%), but different structures called G A (a 3-α helix fold) and G B (an α/β fold). The analysis, based on 132 site-directed mutants, is fully consistent with the idea that protein topology is committed very early along the pathway of folding. Furthermore, data reveals that when folding approaches a perfect two-state scenario, as in the case of the G A domains, the structural features of the transition state appear very robust to changes in sequence composition. On the other hand, when folding is more complex and multistate, as for the G Bs, there are alternative nuclei or accessible pathways that can be alternatively stabilized by altering the primary structure. The implications of our results in the light of previous work on the folding of different members belonging to the same protein family are discussed

Three-point functions in N = 4 Yang-Mills theory and pp-waves

Recently it has been proposed that the coefficient of the three-point function of the BMN operators in = 4 supersymmetric Yang-Mills theory is related to the three-string interactions in the pp-wave background. We calculate three-point functions of these operators to the first order in the effective Yang-Mills coupling λ' = gYM2N/J2 in planar perturbation theory. On the string theory side, we derive the explicit expressions of the Neumann matrices to all orders in 1/(μp+α')2. This allows us to compute the corresponding three-string scattering amplitudes. This provides an all orders prediction for the field theory three-point functions. We compare our field theory results with the string theory results to the subleading order in 1/(μp+α')2 and find perfect agreement

Structural investigation of nucleophosmin interaction with the tumor suppressor Fbw7γ

Nucleophosmin (NPM1) is a multifunctional nucleolar protein implicated in ribogenesis, centrosome duplication, cell cycle control, regulation of DNA repair and apoptotic response to stress stimuli. The majority of these functions are played through the interactions with a variety of protein partners. NPM1 is frequently overexpressed in solid tumors of different histological origin. Furthermore NPM1 is the most frequently mutated protein in acute myeloid leukemia (AML) patients. Mutations map to the C-terminal domain and lead to the aberrant and stable localization of the protein in the cytoplasm of leukemic blasts. Among NPM1 protein partners, a pivotal role is played by the tumor suppressor Fbw7γ, an E3-ubiquitin ligase that degrades oncoproteins like c-MYC, cyclin E, Notch and c-jun. In AML with NPM1 mutations, Fbw7γ is degraded following its abnormal cytosolic delocalization by mutated NPM1. This mechanism also applies to other tumor suppressors and it has been suggested that it may play a key role in leukemogenesis. Here we analyse the interaction between NPM1 and Fbw7γ, by identifying the protein surfaces implicated in recognition and key aminoacids involved. Based on the results of computational methods, we propose a structural model for the interaction, which is substantiated by experimental findings on several site-directed mutants. We also extend the analysis to two other NPM1 partners (HIV Tat and CENP-W) and conclude that NPM1 uses the same molecular surface as a platform for recognizing different protein partners. We suggest that this region of NPM1 may be targeted for cancer treatment

Complete form factors in Yang-Mills from unitarity and spinor helicity in six dimensions

We present a systematic procedure to compute complete, analytic form factors of gauge-invariant operators at loop level in pure Yang-Mills. We consider applications to operators of the form $\mathrm{Tr}\, F^n$ where $F$ is the gluon field strength. Our approach is based on an extension to form factors of the dimensional reconstruction technique, in conjunction with the six-dimensional spinor-helicity formalism and generalised unitarity. For form factors this technique requires the introduction of additional scalar operators, for which we provide a systematic prescription. We also discuss a generalisation of dimensional reconstruction to any number of loops, both for amplitudes and form factors. Several novel results for one-loop minimal and non-minimal form factors of $\mathrm{Tr}\, F^n$ with $n>2$ are presented. Finally, we describe the \texttt{Mathematica} package \texttt{SpinorHelicity6D}, which is tailored to handle six-dimensional quantities written in the spinor-helicity formalism.Comment: 56 page

Note on the absence of R-2 corrections to Newton's potential

We consider Einstein gravity with the addition of $R^2$ and $R^{\mu \nu} R_{\mu \nu}$ interactions in the context of effective field theory, and the corresponding scattering amplitudes of gravitons and minimally-coupled heavy scalars. First, we recover the known fact that graviton amplitudes are the same as in Einstein gravity. Then we show that all amplitudes with two heavy scalars and an arbitrary number of gravitons are also not affected by these interactions. We prove this by direct computations, using field redefinitions known from earlier applications in string theory, and with a combination of factorisation and power-counting arguments. Combined with unitarity, these results imply that, in an effective field theory approach, the Newtonian potential receives neither classical nor quantum corrections from terms quadratic in the curvature.Comment: 15 page

From amplitudes to gravitational radiation with cubic interactions and tidal effects

We study the effect of cubic and tidal interactions on the spectrum of gravitational waves emitted in the inspiral phase of the merger of two nonspinning objects. There are two independent parity-even cubic interaction terms, which we take to be I 1 = R α β μ ν R μ ν ρ σ R ρ σ α β and G 3 = I 1 − 2 R α μ β ν R μ ρ ν σ R ρ α σ β . The latter has vanishing pure graviton amplitudes but modifies mixed scalar/graviton amplitudes which are crucial for our study. Working in an effective field theory setup, we compute the modifications to the quadrupole moment due to I 1 , G 3 and tidal interactions, from which we obtain the power of gravitational waves radiated in the process to first order in the perturbations and leading order in the post-Minkowskian expansion. The I 1 predictions are novel, and we find that our results for G 3 are related to the known quadrupole corrections arising from tidal perturbations, although the physical origin of the G 3 coupling is unrelated to the finite-size effects underlying tidal interactions. We show this by recomputing such tidal corrections and by presenting an explicit field redefinition. In the post-Newtonian expansion our results are complete at leading order, which for the gravitational-wave flux is 5PN for G 3 and tidal interactions and 6PN for I 1 . Finally, we compute the corresponding modifications to the waveforms

The role of a disulfide bridge in the stability and folding kinetics of Arabidopsis thaliana cytochrome c6A

Cytochrome c 6A is a eukaryotic member of the Class I cytochrome c family possessing a high structural homology with photosynthetic cytochrome c 6 from cyanobacteria, but structurally and functionally distinct through the presence of a disulfide bond and a heme mid-point redox potential of + 71 mV (vs normal hydrogen electrode). The disulfide bond is part of a loop insertion peptide that forms a cap-like structure on top of the core α-helical fold. We have investigated the contribution of the disulfide bond to thermodynamic stability and (un)folding kinetics in cytochrome c 6A from Arabidopsis thaliana by making comparison with a photosynthetic cytochrome c 6 from Phormidium laminosum and through a mutant in which the Cys residues have been replaced with Ser residues (C67/73S). We find that the disulfide bond makes a significant contribution to overall stability in both the ferric and ferrous heme states. Both cytochromes c 6A and c 6 fold rapidly at neutral pH through an on-pathway intermediate. The unfolding rate for the C67/73S variant is significantly increased indicating that the formation of this region occurs late in the folding pathway. We conclude that the disulfide bridge in cytochrome c 6A acts as a conformational restraint in both the folding intermediate and native state of the protein and that it likely serves a structural rather than a previously proposed catalytic role. © 2011 Elsevier B.V. All rights reserved

Direct imaging of defect formation in strained organic flexible electronics by Scanning Kelvin Probe Microscopy

The development of new materials and devices for flexible electronics depends crucially on the understanding of how strain affects electronic material properties at the nano-scale. Scanning Kelvin-Probe Microscopy (SKPM) is a unique technique for nanoelectronic investigations as it combines non-invasive measurement of surface topography and surface electrical potential. Here we show that SKPM in non-contact mode is feasible on deformed flexible samples and allows to identify strain induced electronic defects. As an example we apply the technique to investigate the strain response of organic thin film transistors containing TIPS-pentacene patterned on polymer foils. Controlled surface strain is induced in the semiconducting layer by bending the transistor substrate. The amount of local strain is quantified by a mathematical model describing the bending mechanics. We find that the step-wise reduction of device performance at critical bending radii is caused by the formation of nano-cracks in the microcrystal morphology of the TIPS-pentacene film. The cracks are easily identified due to the abrupt variation in SKPM surface potential caused by a local increase in resistance. Importantly, the strong surface adhesion of microcrystals to the elastic dielectric allows to maintain a conductive path also after fracture thus providing the opportunity to attenuate strain effects