The synthesis of recombinant membrane proteins in yeast for structural studies

Historically, recombinant membrane protein production has been a major challenge meaning that many fewer membrane protein structures have been published than those of soluble proteins. However, there has been a recent, almost exponential increase in the number of membrane protein structures being deposited in the Protein Data Bank. This suggests that empirical methods are now available that can ensure the required protein supply for these difficult targets. This review focuses on methods that are available for protein production in yeast, which is an important source of recombinant eukaryotic membrane proteins. We provide an overview of approaches to optimize the expression plasmid, host cell and culture conditions, as well as the extraction and purification of functional protein for crystallization trials in preparation for structural studies

Role of electrostatic interactions in amyloid beta-protein (Abeta) oligomer formation: A discrete molecular dynamics study

Pathological folding and oligomer formation of the amyloid beta-protein (Abeta) are widely perceived as central to Alzheimer's disease (AD). Experimental approaches to study Abeta self-assembly are problematic, because most relevant aggregates are quasi-stable and inhomogeneous. We apply a discrete molecular dynamics (DMD) approach combined with a four-bead protein model to study oligomer formation of the amyloid beta-protein (Abeta). We address the differences between the two most common Abeta alloforms, Abeta40 and Abeta42, which oligomerize differently in vitro. We study how the presence of electrostatic interactions (EIs) between pairs of charged amino acids affects Abeta40 and Abeta42 oligomer formation. Our results indicate that EIs promote formation of larger oligomers in both Abeta40 and Abeta42. The Abeta40 size distribution remains unimodal, whereas the Abeta42 distribution is trimodal, as observed experimentally. Abeta42 folded structure is characterized by a turn in the C-terminus that is not present in Abeta40. We show that the same C-terminal region is also responsible for the strongest intermolecular contacts in Abeta42 pentamers and larger oligomers. Our results suggest that this C-terminal region plays a key role in the formation of Abeta42 oligomers and the relative importance of this region increases in the presence of EIs. These results suggest that inhibitors targeting the C-terminal region of Abeta42 oligomers may be able to prevent oligomer formation or structurally modify the assemblies to reduce their toxicity.Comment: Accepted for publication at Biophysical Journa

Generalizations of Gronwall-Bihari Inequalities on Time Scales

We establish some nonlinear integral inequalities for functions defined on a time scale. The results extend some previous Gronwall and Bihari type inequalities on time scales. Some examples of time scales for which our results can be applied are provided. An application to the qualitative analysis of a nonlinear dynamic equation is discussed.Comment: This is a preprint of an article accepted (16/May/2008) for publication in the "Journal of Difference Equations and Applications"; J. Difference Equ. Appl. is available online at http://www.informaworld.co

A signal theory approach to support vector classification: the sinc kernel

Fourier-based regularisation is considered for the support vector machine classification problem over absolutely integrable loss functions. By invoking the modest assumption that the decision function belongs to a Paley–Wiener space, it is shown that the classification problem can be developed in the context of signal theory. Furthermore, by employing the Paley–Wiener reproducing kernel, namely the sinc function, it is shown that a principled and finite kernel hyper-parameter search space can be discerned, a priori. Subsequent simulations performed on a commonly-available hyperspectral image data set reveal that the approach yields results that surpass state-of-the-art benchmarks

Causal categories: relativistically interacting processes

A symmetric monoidal category naturally arises as the mathematical structure that organizes physical systems, processes, and composition thereof, both sequentially and in parallel. This structure admits a purely graphical calculus. This paper is concerned with the encoding of a fixed causal structure within a symmetric monoidal category: causal dependencies will correspond to topological connectedness in the graphical language. We show that correlations, either classical or quantum, force terminality of the tensor unit. We also show that well-definedness of the concept of a global state forces the monoidal product to be only partially defined, which in turn results in a relativistic covariance theorem. Except for these assumptions, at no stage do we assume anything more than purely compositional symmetric-monoidal categorical structure. We cast these two structural results in terms of a mathematical entity, which we call a `causal category'. We provide methods of constructing causal categories, and we study the consequences of these methods for the general framework of categorical quantum mechanics.Comment: 43 pages, lots of figure

Sum rules and energy scales in the high-temperature superconductor YBa2Cu3O6+x

The Ferrell-Glover-Tinkham (FGT) sum rule has been applied to the temperature dependence of the in-plane optical conductivity of optimally-doped YBa_2Cu_3O_{6.95} and underdoped YBa_2Cu_3O_{6.60}. Within the accuracy of the experiment, the sum rule is obeyed in both materials. However, the energy scale \omega_c required to recover the full strength of the superfluid \rho_s in the two materials is dramatically different; \omega_c \simeq 800 cm^{-1} in the optimally doped system (close to twice the maximum of the superconducting gap, 2\Delta_0), but \omega_c \gtrsim 5000 cm^{-1} in the underdoped system. In both materials, the normal-state scattering rate close to the critical temperature is small, \Gamma < 2\Delta_0, so that the materials are not in the dirty limit and the relevant energy scale for \rho_s in a BCS material should be twice the energy gap. The FGT sum rule in the optimally-doped material suggests that the majority of the spectral weight of the condensate comes from energies below 2\Delta_0, which is consistent with a BCS material in which the condensate originates from a Fermi liquid normal state. In the underdoped material the larger energy scale may be a result of the non-Fermi liquid nature of the normal state. The dramatically different energy scales suggest that the nature of the normal state creates specific conditions for observing the different aspects of what is presumably a central mechanism for superconductivity in these materials.Comment: RevTeX 4 file, 9 pages with 7 embedded eps figure

Neutrinoless double-beta decay and effective field theory

We analyze neutrinoless double $\beta$-decay (\nbb-decay) mediated by heavy particles from the standpoint of effective field theory. We show how symmetries of the \nbb-decay quark operators arising in a given particle physics model determine the form of the corresponding effective, hadronic operators. We classify the latter according to their symmetry transformation properties as well as the order at which they appear in a derivative expansion. We apply this framework to several particle physics models, including R-parity violating supersymmetry (RPV SUSY) and the left-right symmetric model (LRSM) with mixing and a right-handed Majorana neutrino. We show that, in general, the pion exchange contributions to \nbb-decay dominate over the short-range four-nucleon operators. This confirms previously published RPV SUSY results and allows us to derive new constraints on the masses in the LRSM. In particular, we show how a non-zero mixing angle $\zeta$ in the left-right symmetry model produces a new potentially dominant contribution to \nbb-decay that substantially modifies previous limits on the masses of the right-handed neutrino and boson stemming from constraints from \nbb-decay and vacuum stability requirements.Comment: 37 pages. Accepted for publication in PR

Microwave determination of the quasiparticle scattering time in YBa2Cu3O6.95

We report microwave surface resistance (Rs) measurements on two very-high-quality YBa2Cu3O6.95 crystals which exhibit extremely low residual loss at 1.2 K (2-6 μΩ at 2 GHz), a broad, reproducible peak at around 38 K, and a rapid increase in loss, by 4 orders of magnitude, between 80 and 93 K. These data provide one ingredient in the determination of the temperature dependence of the real part of the microwave conductivity, σ1(T), and of the quasiparticle scattering time. The other necessary ingredient is an accurate knowledge of the magnitude and temperature dependence of the London penetration depth, λ(T). This is derived from published data, from microwave data of Anlage, Langley, and co-workers and from, high-quality μSR data. We infer, from a careful analysis of all available data, that λ2(0)/λ2(T) is well approximated by the simple function 1-t2, where t=T/Tc, and that the low-temperature data are incompatible with the existence of an s-wave, BCS-like gap. Combining the Rs and λ(T) data, we find that σ1(T), has a broad peak around 32 K with a value about 20 times that at Tc. Using a generalized two-fluid model, we extract the temperature dependence of the quasiparticle scattering rate which follows an exponential law, exp(T/T0), where T0≊12 K, for T between 15 and 84 K. Such a temperature dependence has previously been observed in measurements of the nuclear spin-lattice relaxation rate. Both the uncertainties in our analysis and the implications for the mechanism of high-temperature superconductivity are discussed

Avaliação do impacto da suplementação alimentar a gestantes no cotrole do baixo peso ao nascer no município de São Paulo, SP (Brasil)

A partir de estudo realizado em oito grandes maternidades do Município de São Paulo, SP (Brasil) que atendem clientela predominantemente de baixo nível sócio-econômico, objetivou-se analisar o impacto da suplementação alimentar durante a assistência pré-natal sobre a incidência de recém-nascidos de baixo peso ao nascer (peso < 2.500 g). Foram envolvidos no estudo 1.060 recém-nascidos de mães que receberam suplementação e 664 recém-nascidos de mães que não a receberam. Ã incidência de baixo peso ao nascer foi de cerca de 11%, considerada elevada e semelhante em ambos os grupos de recém-nascidos. A análise multivariada, realizada para controlar eventuais diferenças entre os grupos, que não a condição de suplementação, descartou qualquer associação significativa entre suplementação e peso ao nascer e revelou, por outro lado, que tabagismo e morbidade na gestação e determinadas características antropométricas e reprodutivas da mãe, prévias à gestação, são importantes fatores de risco para o baixo peso ao nascer. A aparente explicação para a ausência de impacto da suplementação alimentar na população estudada parece residir não na quantidade insuficiente da suplementação alimentar oferecida (370 Kcal/dia), mas no predomínio de fatores não alimentares na determinação do baixo peso ao nascer. São formuladas recomendações quanto ao controle do baixo peso ao nascer no contexto estudado