The Prefusogenic Intermediate of HIV-1 gp41 Contains Exposed C-peptide Regions

The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein is composed of a complex between the surface subunit gp120, which binds to cellular receptors, and the transmembrane subunit gp41. Upon activation of the envelope glycoprotein by cellular receptors, gp41 undergoes conformational changes that mediate fusion of the viral and cellular membranes. Prior to formation of a fusogenic "trimer-of-hairpins" structure, gp41 transiently adopts a prefusogenic conformation whose structural features are poorly understood. An important approach toward understanding structural conformations of gp41 during HIV-1 entry has been to analyze the structural targets of gp41 inhibitors. We have constructed epitope-tagged versions of 5-Helix, a designed protein that binds to the C-peptide region of gp41 and inhibits HIV-1 membrane fusion. Using these 5-Helix variants, we examined which conformation of gp41 is the target of 5-Helix. We find that although 5-Helix binds poorly to native gp41, it binds strongly to gp41 activated by interaction of the envelope protein with either soluble CD4 or membrane-bound cellular receptors. This preferential interaction with activated gp41 results in the accumulation of 5-Helix on the surface of activated cells. These results strongly suggest that the gp41 prefusogenic intermediate is the target of 5-Helix and that this intermediate has a remarkably "open" structure, with exposed C-peptide regions. These results provide important structural information about this intermediate that should facilitate the development of HIV-1 entry inhibitors and may lead to new vaccine strategies

Air-core photonic band-gap fibers: the impact of surface modes

We study the dispersion and leakage properties for the recently reported low-loss photonic band-gap fiber by Smith et al. [Nature 424, 657 (2003)]. We find that surface modes have a significant impact on both the dispersion and leakage properties of the fundamental mode. Our dispersion results are in qualitative agreement with the dispersion profile reported recently by Ouzounov et al. [Science 301, 1702 (2003)] though our results suggest that the observed long-wavelength anomalous dispersion is due to an avoided crossing (with surface modes) rather than band-bending caused by the photonic band-gap boundary of the cladding.Comment: 7 pages including 4 figures. Accepted for Optics Expres

Linear Programming Relaxations for Goldreich's Generators over Non-Binary Alphabets

Goldreich suggested candidates of one-way functions and pseudorandom generators included in $\mathsf{NC}^0$. It is known that randomly generated Goldreich's generator using $(r-1)$-wise independent predicates with $n$ input variables and $m=C n^{r/2}$ output variables is not pseudorandom generator with high probability for sufficiently large constant $C$. Most of the previous works assume that the alphabet is binary and use techniques available only for the binary alphabet. In this paper, we deal with non-binary generalization of Goldreich's generator and derives the tight threshold for linear programming relaxation attack using local marginal polytope for randomly generated Goldreich's generators. We assume that $u(n)\in \omega(1)\cap o(n)$ input variables are known. In that case, we show that when $r\ge 3$, there is an exact threshold $\mu_\mathrm{c}(k,r):=\binom{k}{r}^{-1}\frac{(r-2)^{r-2}}{r(r-1)^{r-1}}$ such that for $m=\mu\frac{n^{r-1}}{u(n)^{r-2}}$, the LP relaxation can determine linearly many input variables of Goldreich's generator if $\mu>\mu_\mathrm{c}(k,r)$, and that the LP relaxation cannot determine $\frac1{r-2} u(n)$ input variables of Goldreich's generator if $\mu<\mu_\mathrm{c}(k,r)$. This paper uses characterization of LP solutions by combinatorial structures called stopping sets on a bipartite graph, which is related to a simple algorithm called peeling algorithm.Comment: 14 pages, 1 figur

Ultrastructure and biochemical function of the mitochondria in respiratory-deficient mutant yeast induced by 4-nitroquinoline nitrogen oxide

1. A respiratory-deficient mutant strain of yeast was obtained from wild strain of Saccharomyces servisiae by treatment with 4-nitroquinoline N-oxide. Ultrastructure and function of the wild or mutant strains and the mitochondrial fractions isolated from these strains were examined by biochemical and electron microscopic analyses. 2. The frequency of the respiratory-deficient mutant strain in yeast induced with 10-6M 4-nitroquinoline N-oxide was about 40 %. 3. Respiratory-deficient mutant strain is incapable of reducing 2, 3, 5-triphenyltetrazolium chloride salt and to grow on lactate medium. In addition to this, the mutant has been found to have lost its ability to take up oxygen in sodium succinate and pyruvate. 4. 4.Nitroquinoline N-oxide in the concentration that induces a mutant of yeast cells or its kin inhibits the oxygen uptake in normal strain. 5. The normal strain of yeast is characterized by difference spectrum corresponding to cytochromes a+as, band c+Cll respectively, whereas, the mutant strain containes almost no cytochromes a+ as, band C1 but contains normal or increased amount of cytochrome c. 6. Mitochondrial fraction isolated from mutant strain has largely lost its ability to oxidize succinate. On the other hand, NADH-, lactate-and cytochrome c-oxidase activities are reduced by about 1/17, 1/7 and 1/8 of that of normal strain, respectively. 7. Succinate dehydrogenase activity of mutant strain is almost zero. Moreover, this activity is not affected on the addition of phenazine methosulfate. NADH dehydrogenase activity of mutant stran is about 1/2 of normal strain. 8. The variations in mitochondrial structure of normal and mutant strain in the stationary phase have been followed with the aid of electron microscopy. In contrast to the normal strain, the mutant strain revealed distinct morphological changes in mitochondria, especially, the lack of cristae in its interior. The results have been interpreted to indicate that the mutant induced by 4.nitroquinoline N.oxide has a character of cyto. plasmic mutant.</p

Endlessly single-mode holey fibers: the influence of core design

In this paper we evaluate the cut-off properties of holey fibers (HFs) with a triangular lattice of air holes and the core formed by the removal of a single (HF1) or more air holes (HF3 and HF7). With the aid of finite-element simulations we determine the single-mode and multi-mode phases and also find the air hole diameters limiting the endlessly single-mode regime. From calculations of V and W parameters we find that in general HF1 is less susceptible to longitudinal non-uniformities compared to the other designs for equivalent effective areas. As an example we illustrate this general property for the particular case of a macro-bending induced loss.Comment: 7 pages including 4 figures. Accepted for Opt. Expres