Broad neutralization coverage of HIV by multiple highly potent antibodies

Broadly neutralizing antibodies against highly variable viral pathogens are much sought after to treat or protect against global circulating viruses. Here we probed the neutralizing antibody repertoires of four human immunodeficiency virus (HIV)-infected donors with remarkably broad and potent neutralizing responses and rescued 17 new monoclonal antibodies that neutralize broadly across clades. Many of the new monoclonal antibodies are almost tenfold more potent than the recently described PG9, PG16 and VRC01 broadly neutralizing monoclonal antibodies and 100-fold more potent than the original prototype HIV broadly neutralizing monoclonal antibodies. The monoclonal antibodies largely recapitulate the neutralization breadth found in the corresponding donor serum and many recognize novel epitopes on envelope (Env) glycoprotein gp120, illuminating new targets for vaccine design. Analysis of neutralization by the full complement of anti-HIV broadly neutralizing monoclonal antibodies now available reveals that certain combinations of antibodies should offer markedly more favourable coverage of the enormous diversity of global circulating viruses than others and these combinations might be sought in active or passive immunization regimes. Overall, the isolation of multiple HIV broadly neutralizing monoclonal antibodies from several donors that, in aggregate, provide broad coverage at low concentrations is a highly positive indicator for the eventual design of an effective antibody-based HIV vaccine.     

A lamprey from the Devonian period of South Africa

Lampreys are the most scientifically accessible of the remaining jawless vertebrates, but their evolutionary history is obscure. In contrast to the rich fossil record of armoured jawless fishes, all of which date from the Devonian period and earlier, only two Palaeozoic lampreys have been recorded, both from the Carboniferous period. In addition to these, the recent report of an exquisitely preserved Lower Cretaceous example demonstrates that anatomically modern lampreys were present by the late Mesozoic era. Here we report a marine/estuarine fossil lamprey from the Famennian (Late Devonian) of South Africa, the identity of which is established easily because many of the key specializations of modern forms are already in place. These specializations include the first evidence of a large oral disc, the first direct evidence of circumoral teeth and a well preserved branchial basket. This small agnathan, Priscomyzon riniensis gen. et sp. nov., is not only more conventionally lamprey-like than other Palaeozoic examples, but is also some 35 million years older. This finding is evidence that agnathans close to modern lampreys had evolved before the end of the Devonian period. In this light, lampreys as a whole appear all the more remarkable: ancient specialists that have persisted as such and survived a subsequent 360 million years.     

Big data and prediction: Four case studies

Has the rise of data-intensive science, or ‘big data’, revolutionized our ability to predict? Does it imply a new priority for prediction over causal understanding, and a diminished role for theory and human experts? I examine four important cases where prediction is desirable: political elections, the weather, GDP, and the results of interventions suggested by economic experiments. These cases suggest caution. Although big data methods are indeed very useful sometimes, in this paper's cases they improve predictions either limitedly or not at all, and their prospects of doing so in the future are limited too.     

IT Diffusion,Implementation and Assimilation in Micro-Businesses – an Exploratory Study Based on a Process Approach

An important limitation of the management information systems (MIS) literature concerns the lack of a process model to understand how a system is assimilated by the organization. We seek to contribute to this topic through studying ERP adoption in two Chilean restaurants. In this paper is proposed that adoption occurs as a process composed of four stages and, therefore, it is presented findings from three of them. We used action-research (AR) as a methodological framework. Two AR cycles were performed in each case. Qualitative data was collected from the field through video recording, interviews, observation and social network analysis. Analysis data was analyzed by comparing results within-cases and between-cases. Three conclusions were reached: (1) during the implementation, a user-system negotiation cycle occurs; (2) after assimilating, the system must be constantly confirmed, otherwise can be abandoned; (3) speed of assimilation by group users depends of degree of influence in the social group of early adopters. Interestingly, an innovative micro-business owner could become a barrier to successful assimilation of a system. Findings introduce a dissenting view to most studies that have found that involvement of management is always beneficial to the success of a technology project. Our findings show involvement of owner impacts a successful adoption, but this impact is not because that person is the owner, but because of their degree of influence on the social group. Conclusions of this study will be of interest to micro, small and medium-business owners because it shows the value of social structure of the organization as a determinant of the success of a technological project.     

Thomas Harriot’s optics,between experiment and imagination: the case of Mr Bulkeley’s glass

Some time in the late 1590s, the Welsh amateur mathematician John Bulkeley wrote to Thomas Harriot asking his opinion about the properties of a truly gargantuan (but totally imaginary) plano-spherical convex lens, 48 feet in diameter. While Bulkeley’s original letter is lost, Harriot devoted several pages to the optical properties of “Mr Bulkeley his Glasse” in his optical papers (now in British Library MS Add. 6789), paying particular attention to the place of its burning point. Harriot’s calculational methods in these papers are almost unique in Harriot’s optical remains, in that he uses both the sine law of refraction and interpolation from Witelo’s refraction tables in order to analyze the passage of light through the glass. For this and other reasons, it is very likely that Harriot wrote his papers on Bulkeley’s glass very shortly after his discovery of the law and while still working closely with Witelo’s great Optics; the papers represent, perhaps, his very first application of the law. His and Bulkeley’s interest in this giant glass conform to a long English tradition of curiosity about the optical and burning properties of large glasses, which grew more intense in late sixteenth-century England. In particular, Thomas Digges’s bold and widely known assertions about his father’s glasses that could see things several miles distant and could burn objects a half-mile or further away may have attracted Harriot and Bulkeley’s skeptical attention; for Harriot’s analysis of the burning distance and the intensity of Bulkeley’s fantastic lens, it shows that Digges’s claims could never have been true about any real lens (and this, I propose, was what Bulkeley had asked about in his original letter to Harriot). There was also a deeper, mathematical relevance to the problem that may have caught Harriot’s attention. His most recent source on refraction—Giambattista della Porta’s De refractione of 1593—identified a mathematical flaw in Witelo’s cursory suggestion about the optics of a lens (the only place that lenses appear, however fleetingly, in the writings of the thirteenth-century Perspectivist authors). In his early notes on optics, in a copy of Witelo’s optics, Harriot highlighted Witelo’s remarks on the lens and della Porta’s criticism (which he found unsatisfactory). The most significant problem with Witelo’s theorem would disappear as the radius of curvature of the lens approached infinity. Bulkeley’s gigantic glass, then, may have provided Harriot an opportunity to test out Witelo’s claims about a plano-spherical glass, at a time when he was still intensely concerned with the problems and methods of the Perspectivist school.     

The cyclin-dependent kinase family in the social amoebozoan Dictyostelium discoideum

Cyclin-dependent kinases (Cdk) are a family of serine/threonine protein kinases that regulate eukaryotic cell cycle progression. Their ability to modulate the cell cycle has made them an attractive target for anti-cancer therapies. Cdk protein function has been studied in a variety of Eukaryotes ranging from yeast to humans. In the social amoebozoan Dictyostelium discoideum, several homologues of mammalian Cdks have been identified and characterized. The life cycle of this model organism is comprised of a feeding stage where single cells grow and divide mitotically as they feed on their bacterial food source and a multicellular developmental stage that is induced by starvation. Thus it is a valuable system for studying a variety of cellular and developmental processes. In this review I summarize the current knowledge of the Cdk protein family in Dictyostelium by highlighting the research efforts focused on the characterization of Cdk1, Cdk5, and Cdk8 in this model Eukaryote. Accumulated evidence indicates that each protein performs distinct functions during the Dictyostelium life cycle with Cdk1 being required for growth and Cdk5 and Cdk8 being required for processes that occur during development. Recent studies have shown that Dictyostelium Cdk5 shares attributes with mammalian Cdk5 and that the mammalian Cdk inhibitor roscovitine can be used to inhibit Cdk5 activity in Dictyostelium. Together, these results show that Dictyostelium can be used as a model system for studying Cdk protein function.     

Evaluation of the Heat,Entropy, and Rotational Changes Produced by Gravitational Segregation during Core Formation

Core formation by gravitational segregation allegedly released sufficient interior heat to melt the Earth. Analysis of the energetics, which compare gravitational potential energy (Ug) of a fictitious,...     

Microhabitat selection by the johnny darter, Etheostoma nigrum Rafinesque, in a Wyoming stream

Microhabitat selection by the johnny darter ( Etheostoma nigrum ) was examined in the North Laramie River, Platte County, Wyoming, where it does not occur with other darter species in the same stream reach. Electivity indices based on microhabitat observations indicate that E. nigrum avoids riffles and selects certain microhabitats characterized by intermediate water depths in pools and slow-moving runs with a substrate composed primarily of silt and sand. Niche breadth and electivity values for total depth, bottom water velocity, and substrate measurements from this study indicate that E. nigrum is a habitat generalist, except at the extreme ends of the habitat gradient. Habitat use here is generally similar to other studies where E. nigrum occurred with one or more other darter species. This study found little evidence for competitive release in the absence of other darters.