Emergent properties of the interferon-signalling network may underlie the success of hepatitis C treatment

Current interferon alpha-based treatment of hepatitis C virus (HCV) infection fails to cure a sizeable fraction of patients treated. The cause of this treatment failure remains unknown. Here using mathematical modelling, we predict treatment failure to be a consequence of the emergent properties of the interferon-signalling network. HCV induces bistability in the network, creating a new steady state where it can persist. Cells that admit the new steady state alone are refractory to interferon. Using a model of viral kinetics, we show that when the fraction of cells refractory to interferon in a patient exceeds a critical value, treatment fails. Direct-acting antivirals that suppress HCV replication can eliminate the new steady state, restoring interferon sensitivity and improving treatment response. Our study thus presents a new conceptual basis of HCV persistence and treatment response, elucidates the origin of the synergy between interferon and direct-acting antivirals, and facilitates rational treatment optimization.

Histone H3K9 acetylation level modulates gene expression and may affect parasite growth in human malaria parasite Plasmodium falciparum

Three-dimensional positioning of the nuclear genome plays an important role in the epigenetic regulation of genes. Although nucleographic domain compartmentalization in the regulation of epigenetic state and gene expression is well established in higher organisms, it remains poorly understood in the pathogenic parasite Plasmodium falciparum. In the present study, we report that two histone tail modifications, H3K9Ac and H3K14Ac, are differentially distributed in the parasite nucleus. We find colocalization of active gene promoters such as Tu1 (tubulin-1 expressed in the asexual stages) with H3K9Ac marks at the nuclear periphery. By contrast, asexual stage inactive gene promoters such as Pfg27 (gametocyte marker) and Pfs28 (ookinete marker) occupy H3K9Ac devoid zones at the nuclear periphery. The histone H3K9 is predominantly acetylated by the PCAF/GCN5 class of lysine acetyltransferases, which is well characterized in the parasite. Interestingly, embelin, a specific inhibitor of PCAF/GCN5 family histone acetyltransferase, selectively decreases total H3K9Ac acetylation levels (but not H3K14Ac levels) around the var gene promoters, leading to the downregulation of var gene expression, suggesting interplay among histone acetylation status, as well as subnuclear compartmentalization of different genes and their activation in the parasites. Finally, we found that embelin inhibited parasitic growth at the low micromolar range, raising the possibility of using histone acetyltransferases as a target for antimalarial therapy.

OPTIMALITY OF THE PRODUCT-MATRIX CONSTRUCTION FOR SECURE MSR REGENERATING CODES

In this paper, we consider the security of exact-repair regenerating codes operating at the minimum-storage-regenerating (MSR) point. The security requirement (introduced in Shah et. al.) is that no information about the stored data file must be leaked in the presence of an eavesdropper who has access to the contents of l(1) nodes as well as all the repair traffic entering a second disjoint set of l(2) nodes. We derive an upper bound on the size of a data file that can be securely stored that holds whenever l(2) <= d - k +1. This upper bound proves the optimality of the product-matrix-based construction of secure MSR regenerating codes by Shah et. al.

Seismotectonics of the April-May 2015 Nepal earthquakes: An assessment based on the aftershock patterns, surface effects and deformational characteristics

Occurrence of the April 25, 2015 (Mw 7.8) earthquake near Gorkha, central Nepal, and another one that followed on May 12 (Mw 7.3), located similar to 140 km to its east, provides an exceptional opportunity to understand some new facets of Himalayan earthquakes. Here we attempt to assess the seismotectonics of these earthquakes based on the deformational field generated by these events, along with the spatial and temporal characteristics of their aftershocks. When integrated with some of the post-earthquake field observations, including the localization of damage and surface deformation, it became obvious that although the mainshock slip was mostly limited to the Main Himalayan Thrust (MHT), the rupture did not propagate to the Main Frontal Thrust (MFT). Field evidence, supported by the available InSAR imagery of the deformation field, suggests that a component of slip could have emerged through a previously identified out-of-sequence thrust/active thrust in the region that parallels the Main Central Thrust (MCT), known in the literature as a co-linear physiographic transitional zone called PT2. Termination of the first rupture, triggering of the second large earthquake, and distribution of aftershocks are also spatially constrained by the eastern extremity of PT2. Mechanism of the 2015 sequence demonstrates that the out-of-sequence thrusts may accommodate part of the slip, an aspect that needs to be considered in the current understanding of the mechanism of earthquakes originating on the MHT. (c) 2015 Elsevier Ltd. All rights reserved.

Preliminary Analysis on the May 1st Landslide at Wulong

分析了边坡工程地质条件和地质成因机制；根据现场调查数据建立了滑坡地质剖面,反演了滑坡发生时滑动面的抗剪强度参数；分析了原坡形及降雨所引起孔隙水压力对其稳定性的影响,并以反演获得的强度参数结合类似边坡岩体结构面强度试验统计结果,对原边坡进行了可靠度分析,获得了原边坡的潜在破坏概率,从而又在定量角度上获得了滑坡发生的原因。

Ad valorem housing subsidies may reduce house building

In this paper it is shown that an ad valorem housing subsidy set by a central regulator (or a raise in the ad valorem housing subsidy rate) may reduce the number of houses built in the market and increase the price paid by the buyers of houses. The analysis considers a situation where there is imperfect competition in the housing market and a local regulator that decides on density, or on the number of sites for housing development, and that cares about a combination of the profits of housing developers and the surplus of buyers of houses.

Panama Canal Review: Special edition Panama

Leonard Carpenter Panama Canal Collection. Publication: Panama Canal Review Special Edition. [Box 1] from the Special Collections & Area Studies Department, George A. Smathers Libraries, University of Florida. This special edition features articles on Panama reprinted from THE PANAMA CANAL REVIEW, which began publication May 5, 1950. These articles, for which there have been many requests for reprints, have been selected from issues published between 1965 and 1973. Review articles may be reprinted without further clearance (69 page document)

Bulletin of the Department of Agriculture, State of California, May 1939

Includes Exotic Mollusca in California, by G. Dallas Hanna p.298-321.(PDF contains 57 pages.)