Designability of alpha-helical Proteins

A typical protein structure is a compact packing of connected alpha-helices and/or beta-strands. We have developed a method for generating the ensemble of compact structures a given set of helices and strands can form. The method is tested on structures composed of four alpha-helices connected by short turns. All such natural four-helix bundles that are connected by short turns seen in nature are reproduced to closer than 3.6 Angstroms per residue within the ensemble. Since structures with no natural counterpart may be targets for ab initio structure design, the designability of each structure in the ensemble -- defined as the number of sequences with that structure as their lowest energy state -- is evaluated using a hydrophobic energy. For the case of four alpha-helices, a small set of highly designable structures emerges, most of which have an analog among the known four-helix fold families, however several novel packings and topologies are identified.Comment: 21 pages, 6 figures, to appear in PNA

Investigation of routes and funnels in protein folding by free energy functional methods

We use a free energy functional theory to elucidate general properties of heterogeneously ordering, fast folding proteins, and we test our conclusions with lattice simulations. We find that both structural and energetic heterogeneity can lower the free energy barrier to folding. Correlating stronger contact energies with entropically likely contacts of a given native structure lowers the barrier, and anticorrelating the energies has the reverse effect. Designing in relatively mild energetic heterogeneity can eliminate the barrier completely at the transition temperature. Sequences with native energies tuned to fold uniformly, as well as sequences tuned to fold by a single or a few routes, are rare. Sequences with weak native energetic heterogeneity are more common; their folding kinetics is more strongly determined by properties of the native structure. Sequences with different distributions of stability throughout the protein may still be good folders to the same structure. A measure of folding route narrowness is introduced which correlates with rate, and which can give information about the intrinsic biases in ordering due to native topology. This theoretical framework allows us to systematically investigate the coupled effects of energy and topology in protein folding, and to interpret recent experiments which investigate these effects.Comment: 12 pages, 1 figure, to appear in Proc. Natl. Acad. Sc

Las especies de Forcipomyia, Meigen (Diptera: Ceratopogonidae) polinizadoras del cacao ( Theobroma cacao L.) en la Colecci\uf3n de la Estaci\uf3n Experimental del INIA-Miranda, Venezuela

S\ue1nchez P, Morillo F, Mun\uf3z W, Soria S, Mar\uedn C. 2001. Species of Forcipomyia, Meigen (Diptera: Ceratopogonidae) that pollinate cacao tree ( Theobroma cacao L.) found in the Insect Collection of Miranda Experimental Station, INIA-Miranda, Venezuela. Entomotropica 16(2):147-148. A list of Forcipomyia Meigen species represented in the insect collection at INIA-Miranda Experimental Station is presented as well as the state name in which they were collected.S\ue1nchez P, Morillo F, Mun\uf3z W, Soria S, Mar\uedn C. 2001. Las especies de Forcipomyia, Meigen (Diptera: Ceratopogonidae) polinizadoras del cacao ( Theobroma cacao L.) en la Colecci\uf3n de la Estaci\uf3n Experimental del INIA-Miranda, Venezuela. Entomotropica 16(2):147-148. Se presenta una lista de especies de Forcipomyia Meigen, representadas en la colecci\uf3n de la Estaci\uf3n Experimental del INIA-Miranda, junto a los estados de Venezuela donde fueron colectadas

Plan de negocio para la elaboraci?n de una bebida instant?nea saborizada a base de leche enriquecida con alb?mina de huevo en Lima Metropolitana

En el siguiente plan de negocios se plantea como objetivo principal determinar la viabilidad t?cnica, econ?mica y financiera para la producci?n y comercializaci?n de una bebida instant?nea saborizada a base de leche enriquecida con alb?mina de huevo en el mercado de Lima Metropolitana. Para el diagn?stico del entorno se utiliz? el an?lisis SEPTE y de cinco fuerzas de Porter evidenciando un entorno favorable para productos enriquecidos. El producto se presentar? en bolsas por 120g con las que se podr? preparar 1 Litro de bebida, adem?s en los sabores de Vainilla y Chocolate. Utilizando encuestas cualitativas y Focus group se determin? la intenci?n e intensidad del mercado y se segment? el mercado objetivo en los NSE B y C. Con este mercado se establece como meta posicionarse en un 4% del mismo, en funci?n de esto se dise?a la cadena de suministro, la cual consiste en un abastecimiento gestionado por la empresa, mientras las operaciones de producci?n, almacenamiento y distribuci?n son tercerizadas con una gesti?n de calidad para supervisarlas. Desarrollando esta operaci?n se obtienen en 5 a?os un VAN Financiero de S/. 449,622.92 y un TIR Financiero de 20.73% con un periodo de retorno del capital de 4 a?os y 3 meses

Remarks on Semileptonic B and D Decays into Orbitally Excited Mesons

We have obtained the differential decay rate and calculated the branching ratios of the exclusive semileptonic decays $B(D) \to Xl\nu$, where $X$ is a p-wave meson, using the nonrelativistic ISGW quark model. Our results are compared with the predictions of the ISGW2 model. We have computed some branching ratios that were not reported or were reported with 0.00 in this model. For example, we find that $Br(B_c^- \to \bar{B_{s2}^{*0}}l^-\bar{\nu}) = 4.03 \times 10^{-5}$, $Br(B_c^- \to \bar{B_2^{*0}}l^- \bar{\nu}) =3.65 \times 10^{-6}$ and $Br(D_s^+ \to f_2l^+\nu) = 2.7 \times 10^{-5}$, which seems to be at the reach of forthcoming experiments. Furthermore, we have classified the $B_{u,d,s} \to Tl\nu$ decays in two groups and compared the semileptonic and nonleptonic decays including a tensor meson in the final state.Comment: 11 pages, LaTe

3D magnetic configuration of ferrimagnetic multilayers with competing interactions visualized by soft X ray vector tomography

Full control of magnetic properties in exchange coupled systems requires a good understanding of 3D magnetic configuration with lateral and in depth resolution. Here we show results from a soft X ray tomographic reconstruction which allow determining, solely from the experimental data, a detailed description of the vector magnetic configuration of a ferrimagnetic Gd12Co88 Nd17Co83 Gd24Co76 trilayer with engineered competing anisotropy, exchange and magneto static interactions at different depths. The trilayer displays chevron patterns with a distorted closure structure. Near the top Gd24Co76 layer, local exchange springs with out of plane magnetization reversal, quasi domains with ripple like patterns and magnetic vortices and antivortices across the thickness are observed. The detailed analysis of the magnetic tomogram shows that the effective strength of the exchange spring at the NdCo GdCo interface can be finely tuned by GdxCo1 x composition and anisotropy determined by sample fabrication and in plane stripe orientation adjustable , demonstrating the suitability of 3D magnetic visualization techniques in magnetic engineering researc

Non-Hermitian SUSY Hydrogen-like Hamiltonians with real spectra

It is shown that the radial part of the Hydrogen Hamiltonian factorizes as the product of two not mutually adjoint first order differential operators plus a complex constant epsilon. The 1-susy approach is used to construct non-hermitian Hamiltonians with hydrogen spectra. Other non-hermitian Hamiltonians are shown to admit an extra `complex energy' at epsilon. New self-adjoint hydrogen-like Hamiltonians are also derived by using a 2-susy transformation with complex conjugate pairs epsilon, (c.c) epsilon.Comment: LaTeX2e file, 13 pages, 6 EPS figures. New references added. The present is a reorganized and simplified versio

Coadministration of Adenoviral Vascular Endothelial Growth Factor and Angiopoietin-1 Enhances Vascularization and Reduces Ventricular Remodeling in the Infarcted Myocardium of Type 1 Diabetic Rats

OBJECTIVE - Hyperglycemia impairs angiogenesis in response to ischemia, leading to ventricular remodeling. Although the effects of overexpressing angiogenic growth factors have been studied in inducing angiogenesis, the formation of functional vessels remains a challenge. The present study evaluates the reversal of diabetes-mediated impairment of angiogenesis in the infarcted diabetic rat myocardium by proangiogenic gene therapy. RESEARCH DESIGN AND METHODS - Ad.VEGF and Ad.Ang1 were intramyocardially administered in combination immediately after myocardial infarction to nondiabetic and diabetic rats. Ad.LacZ was similarly administered to the respective control groups. The hearts were excised for molecular and immunohistochemical analysis at predetermined time points. The myocardial function was measured by echocardiography 30 days after the intervention. RESULTS - We observed reduced fibrosis and increased capillary/arteriolar density along with reduced ventricular remodeling, as assessed by echocardiography in the treated diabetic animals compared with the nontreated diabetic controls. We also observed increased phosphorylated mitogen-activated protein kinase-activated protein kinase-2, 2 days after the treatment and increased expression of vascular endothelial growth factor (VEGF), Flk-1, angiopoietin-1 (Ang-1), Tie-2, and survivin, 4 days after treatment in the diabetic animals. Gel shift analysis revealed that the combination gene therapy stimulated the DNA binding activity of nuclear factor-κB in the diabetic animals. CONCLUSIONS - Our preclinical data demonstrate the efficacy of coadministration of adenoviral VEGF and Ang-1 in increasing angiogenesis and reducing ventricular remodeling in the infarcted diabetic myocardium. These unique results call for the initiation of a clinical trial to assess the efficacy of this therapeutic strategy in the treatment of diabetes-related human heart failure