Hemagglutinin sequence conservation guided stem immunogen design from influenza A H3 subtype

Seasonal epidemics caused by influenza A (H1 and H3 subtypes) and B viruses are a major global health threat. The traditional, trivalent influenza vaccines have limited efficacy because of rapid antigenic evolution of the circulating viruses. This antigenic variability mediates viral escape from the host immune responses, necessitating annual vaccine updates. Influenza vaccines elicit a protective antibody response, primarily targeting the viral surface glycoprotein hemagglutinin (HA). However, the predominant humoral response is against the hypervariable head domain of HA, thereby restricting the breadth of protection. In contrast, the conserved, subdominant stem domain of HA is a potential ``universal'' vaccine candidate. We designed an HA stem-fragment immunogen from the 1968 pandemic H3N2 strain (A/Hong Kong/1/68) guided by a comprehensive H3 HA sequence conservation analysis. The biophysical properties of the designed immunogen were further improved by C-terminal fusion of a trimerization motif, ``isoleucine-zipper'', or ``foldon''. These immunogens elicited cross-reactive, antiviral antibodies and conferred partial protection against a lethal, homologous HK68 virus challenge in vivo. Furthermore, bacterial expression of these immunogens is economical and facilitates rapid scale-up.

Volume conservation issues in incompressible smoothed particle hydrodynamics

A divergence-free velocity field is usually sought in numerical simulations of incompressible fluids. We show that the particle methods that compute a divergence-free velocity field to achieve incompressibility suffer from a volume conservation issue when a finite time-step position update scheme is used. Further, we propose a deformation gradient based approach to arrive at a velocity field that reduces the volume conservation issues in free surface flows and maintains density uniformity in internal flows while retaining the simplicity of first order time updates. (C) 2015 Elsevier Inc. All rights reserved.

Distribution, relative abundance, and conservation status of Asian elephants in Karnataka, southern India

Karnataka state in southern India supports a globally significant and the country's largest population of the Asian elephant Elephas maximus. A reliable map of Asian elephant distribution and measures of spatial variation in their abundance, both vital needs for conservation and management action, are unavailable not only in Karnataka, but across its global range. Here, we use various data gathered between 2000 and 2015 to map the distribution of elephants in Karnataka at the scale of the smallest forest management unit, the `beat', while also presenting data on elephant dung density for a subset of `elephant beats.' Elephants occurred in 972 out of 2855 forest beats of Karnataka. Sixty percent of these 972 beats and 55% of the forest habitat lay outside notified protected areas (PM), and included lands designated for agricultural production and human dwelling. While median elephant dung density inside protected areas was nearly thrice as much as outside, elephants routinely occurred in or used habitats outside PM where human density, land fraction under cultivation, and the interface between human-dominated areas and forests were greater. Based on our data, it is clear that India's framework for elephant conservation which legally protects the species wherever it occurs, but protects only some of its habitats while being appropriate in furthering their conservation within PM, seriously falters in situations where elephants reside in and/or seasonally use areas outside PAs. Attempts to further elephant conservation in production and dwelling areas have extracted high costs in human, elephant, material and monetary terms in Karnataka. In such settings, conservation planning exercises are necessary to determine where the needs of elephants or humans must take priority over the other, and to achieve that in a manner that is based not only on reliable scientific data but also on a process of public reasoning. (C) 2015 Elsevier Ltd. All rights reserved.

Perceptions of priority issues in the conservation of biodiversity and ecosystems in India

We report on the results of a country-wide survey of people's perceptions of issues relating to the conservation of biodiversity and ecosystems in India. Our survey, mainly conducted online, yielded 572 respondents, mostly among educated, urban and sub-urban citizens interested in ecological and environmental issues. 3160 ``raw'' questions generated by the survey were iteratively processed by a group of ecologists, environmental and conservation scientists to produce the primary result of this study: a summarized list of 152 priority questions for the conservation of India's biodiversity and ecosystems, which range across 17 broad thematic classes. Of these, three thematic classes-''Policy and Governance'', ``Biodiversity and Endangered Species'' and ``Protection and Conservation''-accounted for the largest number of questions. A comparative analysis of the results of this study with those from similar studies in other regions brought out interesting regional differences in the thematic classes of questions that were emphasized and suggest that local context plays a large role in determining emergent themes. We believe that the ready list of priority issues generated by this study can be a useful guiding framework for conservation practitioners, researchers, citizens, policy makers and funders to focus their resources and efforts in India's conservation research, action and funding landscape. (C) 2015 Elsevier Ltd. All rights reserved.

Weak conservation of structural features in the interfaces of homologous transient protein-protein complexes

Residue types at the interface of protein-protein complexes (PPCs) are known to be reasonably well conserved. However, we show, using a dataset of known 3-D structures of homologous transient PPCs, that the 3-D location of interfacial residues and their interaction patterns are only moderately and poorly conserved, respectively. Another surprising observation is that a residue at the interface that is conserved is not necessarily in the interface in the homolog. Such differences in homologous complexes are manifested by substitution of the residues that are spatially proximal to the conserved residue and structural differences at the interfaces as well as differences in spatial orientations of the interacting proteins. Conservation of interface location and the interaction pattern at the core of the interfaces is higher than at the periphery of the interface patch. Extents of variability of various structural features reported here for homologous transient PPCs are higher than the variation in homologous permanent homomers. Our findings suggest that straightforward extrapolation of interfacial nature and inter-residue interaction patterns from template to target could lead to serious errors in the modeled complex structure. Understanding the evolution of interfaces provides insights to improve comparative modeling of PPC structures.

The X Chromosome of Hemipteran Insects: Conservation, Dosage Compensation and Sex-Biased Expression

Insects of the order Hemiptera (true bugs) use a wide range of mechanisms of sex determination, including genetic sex determination, paternal genome elimination, and haplodiploidy. Genetic sex determination, the prevalent mode, is generally controlled by a pair of XY sex chromosomes or by an XX/XO system, but different configurations that include additional sex chromosomes are also present. Although this diversity of sex determining systems has been extensively studied at the cytogenetic level, only the X chromosome of the model pea aphid Acyrthosiphon pisum has been analyzed at the genomic level, and little is known about X chromosome biology in the rest of the order. In this study, we take advantage of published DNA- and RNA-seq data from three additional Hemiptera species to perform a comparative analysis of the gene content and expression of the X chromosome throughout this clade. We find that, despite showing evidence of dosage compensation, the X chromosomes of these species show female-biased expression, and a deficit of male-biased genes, in direct contrast to the pea aphid X. We further detect an excess of shared gene content between these very distant species, suggesting that despite the diversity of sex determining systems, the same chromosomal element is used as the X throughout a large portion of the order.

HOMOGENIZATION OF A HYPERBOLIC EQUATION WITH HIGHLY CONTRASTING DIFFUSIVITY COEFFICIENTS

We study a hyperbolic problem in the framework of periodic homogenization assuming a high contrast between the diffusivity coefficients of the two components M-epsilon and B-epsilon of the heterogeneous medium. There are three regimes depending on the ratio between the size of the period and the amplitude a, of the diffusivity in B-epsilon. For the critical regime alpha(epsilon) similar or equal to epsilon, the limit problem is a strongly coupled system involving both the macroscopic and the microscopic variables. We also include the results in the non critical case.

HOMOGENIZATION OF A HYPERBOLIC EQUATION WITH HIGHLY CONTRASTING DIFFUSIVITY COEFFICIENTS

We study a hyperbolic problem in the framework of periodic homogenization assuming a high contrast between the diffusivity coefficients of the two components M-epsilon and B-epsilon of the heterogeneous medium. There are three regimes depending on the ratio between the size of the period and the amplitude a, of the diffusivity in B-epsilon. For the critical regime alpha(epsilon) similar or equal to epsilon, the limit problem is a strongly coupled system involving both the macroscopic and the microscopic variables. We also include the results in the non critical case.

Practical Criterion for Universal Laws and Practical Methods for Construction of Co-variance Sets

给出相对论力学中普遍定律的实用判别法和协变集的实用构造法,还给出实现非普遍定律的“可导出性”的一种实用方法．

A Multimoment Finite-Volume Shallow-Water Model On The Yin-Yang Overset Spherical Grid

A numerical model for shallow-water equations has been built and tested on the Yin-Yang overset spherical grid. A high-order multimoment finite-volume method is used for the spatial discretization in which two kinds of so-called moments of the physical field [i.e., the volume integrated average ( VIA) and the point value (PV)] are treated as the model variables and updated separately in time. In the present model, the PV is computed by the semi-implicit semi-Lagrangian formulation, whereas the VIA is predicted in time via a flux-based finite-volume method and is numerically conserved on each component grid. The concept of including an extra moment (i.e., the volume-integrated value) to enforce the numerical conservativeness provides a general methodology and applies to the existing semi-implicit semi-Lagrangian formulations. Based on both VIA and PV, the high-order interpolation reconstruction can only be done over a single grid cell, which then minimizes the overlapping zone between the Yin and Yang components and effectively reduces the numerical errors introduced in the interpolation required to communicate the data between the two components. The present model completely gets around the singularity and grid convergence in the polar regions of the conventional longitude-latitude grid. Being an issue demanding further investigation, the high-order interpolation across the overlapping region of the Yin-Yang grid in the current model does not rigorously guarantee the numerical conservativeness. Nevertheless, these numerical tests show that the global conservation error in the present model is negligibly small. The model has competitive accuracy and efficiency.

Experimental laws of cratering for hypervelocity impacts of spherical projectiles into thick target

It is shown in this paper that the laws of cratering in a thick target under hypervelocity impact by a spherical projectile can be approximately expressed by the so-called iso-deviation law and a 2/3 power law. Moreover, hypervelocity impact should be characterized by the isotropic expansion of a crater. In the special case, when the projectile and target are of the same material, the laws mentioned above reduce to the result of a semi-spherical crater and the energy criterion. Generally speaking, a semi-spherical crater and the energy criterion are both approximations, which only take projectile density and target strength into account, and can be used for a rough estimation on the order of magnitude. The inconsistency in various fitted power laws in the literature was also clarified and explained in the paper.

Charting multidisciplinary research and action priorities towards the conservation and sustainable management of sea turtles in the Pacific Ocean: a focus on Malaysia

The four sea turtle species found in Malaysia are the leatherback, olive ridley, green and hawksbill. The threats to these species are acute. Populations of leatherback, olive ridley and hawksbill turtles are on the brink of collapse – threatening a biodiversity crisis in Malaysia and the region. This proceedings contains 8 technical papers presented at a workshop convened in Kijal, Terengganu to chart new directions in the conservation of Malaysia's critically endangered sea turtles and to reverse population decline. They represent a wide range of issues from aspects of biology to a review of 40 years of sea turtle conservation. A paper on the socioeconomic linkages and impacts of fisheries was also included as the workshop adopted a multidisciplinary approach to address the issues. Two case studies, including successful restoration examples from international experiences and restoration efforts in Sabah, pave the way for enhancing turtle conservation in the country.