Collective Behaviour without Collective Order in Wild Swarms of Midges

Collective behaviour is a widespread phenomenon in biology, cutting through a huge span of scales, from cell colonies up to bird flocks and fish schools. The most prominent trait of collective behaviour is the emergence of global order: individuals synchronize their states, giving the stunning impression that the group behaves as one. In many biological systems, though, it is unclear whether global order is present. A paradigmatic case is that of insect swarms, whose erratic movements seem to suggest that group formation is a mere epiphenomenon of the independent interaction of each individual with an external landmark. In these cases, whether or not the group behaves truly collectively is debated. Here, we experimentally study swarms of midges in the field and measure how much the change of direction of one midge affects that of other individuals. We discover that, despite the lack of collective order, swarms display very strong correlations, totally incompatible with models of non-interacting particles. We find that correlation increases sharply with the swarm''s density, indicating that the interaction between midges is based on a metric perception mechanism. By means of numerical simulations we demonstrate that such growing correlation is typical of a system close to an ordering transition. Our findings suggest that correlation, rather than order, is the true hallmark of collective behaviour in biological systems.     

Protein crystallization by design: chymotrypsinogen without precipitants

Protein crystals are usually obtained by an empirical approach based on extensive screening to identify suitable crystallization conditions. In contrast, we have used a systematic predictive procedure to produce data-quality crystals of bovine chymotrypsinogen A and used them to obtain a refined X-ray structure to 3 A resolution. Measurements of the osmotic second virial coefficient of chymotrypsinogen solutions were used to identify suitable solvent conditions, following which crystals were grown for approximately 30 hours by ultracentrifugal crystallization, without the use of any precipitants. Existing structures of chymotrypsinogen were obtained in solutions including 10-30 % ethanol, whereas simple buffered NaCl solutions were used here. The protein crystallized in the tetragonal space group P4(1)2(1)2, with one molecule per asymmetric unit. The quality of the refined map was very high throughout, with the main-chain atoms of all but four residues clearly defined and with nearly all side-chains also defined. Although only minor differences are seen compared to the structures previously reported, they indicate the possibility of structural changes due to the crystallization conditions used in those studies. Our results show that more systematic crystallization of proteins is possible, and that the procedure can expand the range of conditions under which crystals can be grown successfully and can make new crystal forms available.     

Order review and release in make-to-order flow shops: analysis and design of new methods

Flexible Services and Manufacturing Journal - Increased customization has strengthened the importance of make-to-order companies. The advent of lean management and the introduction of smart and...     

How evolution generates complexity without design: language as an instructional metaphor

One of the major stumbling blocks to understanding evolution is the difficulty in reconciling the emergence of complexity with the apparently undirected forces that drive evolutionary processes. This difficulty was originally framed as the "Watch and Watchmaker" argument and more recently revived by proponents of "intelligent design." Undergraduates in particular often attribute purpose and forethought as the driving force behind biological phenomena, and have difficulty understanding evolutionary processes. To demonstrate that complexity can arise solely through mutations that fix in populations via natural selection or drift, we can use analogies where processes can be observed across short time frames and where the key data are accessible to those without specialized biological knowledge. The evolution of language provides such an example. Processes of natural selection, mutation, genetic drift, acquisition of new functions, punctuated equilibria, and lateral gene transfer can be illustrated using examples of changing spellings, neologism, and acquisition of words from other languages. The examples presented in this article are readily accessible, and demonstrate to students that languages have dynamically increased in complexity, simply driven by the usage patterns of their speakers.     

Challenges and regulatory experiences with non‐inferiority trial design without placebo arm

For a non‐inferiority trial without a placebo arm, the direct comparison between the test treatment and the selected positive control is in principle the only basis for statistical inference. Therefore, evaluating the test treatment relative to the non‐existent placebo presents extreme challenges and requires some kind of bridging from the past to the present with no current placebo data. For such inference based partly on an indirect bridging manipulation, fixed margin method and synthesis method are the two widely discussed methods in the recent literature. There are major differences in statistical inference paradigm between the two methods. The fixed margin method employs the historical data that assess the performances of the active control versus a placebo to guide the selection of the non‐inferiority margin. Such guidance is not part of the ultimate statistical inference in the non‐inferiority trial. In contrast, the synthesis method connects the historical data to the non‐inferiority trial data for making broader inferences relating the test treatment to the non‐existent current placebo. On the other hand, the type I error rate associated with the direct comparison between the test treatment and the active control cannot shed any light on the appropriateness of the indirect inference for faring the test treatment against the non‐existent placebo. This work explores an approach for assessing the impact of potential bias due to violation of a key statistical assumption to guide determination of the non‐inferiority margin.     

Order and disorder in large multi-site docking proteins of the Gab family--implications for signalling complex formation and inhibitor design strategies

Large multi-site docking (LMD) proteins of the Gab, IRS, FRS, DOK and Cas families consist of one or two folded N-terminal domains, followed by a predominantly disordered C-terminal extension. Their primary function is to provide a docking platform for signalling molecules (including PI3K, PLC, Grb2, Crk, RasGAP, SHP2) in intracellular signal transmission from activated cell-surface receptors, to which they become coupled. A detailed analysis of the structural nature and intrinsic disorder propensity of LMD proteins, with Gab proteins as specific examples, is presented. By primary sequence analysis and literature review the varying levels of disorder and hidden order are predicted, revealing properties and a physical architecture that help to explain their biological function and characteristics, common for network hub proteins. The virulence factor, CagA, from Helicobacter pylori is able to mimic Gab function once injected by this human pathogen into stomach epithelial cells. Its predicted differential structure is compared to Gab1 with respect to its functional mimicry. Lastly, we discuss how LMD proteins, in particular Gab1 and Gab2, and their protein partners, such as SH2 and SH3 domain-containing adaptors like Grb2, might qualify for future anti-cancer strategies in developing protein-protein interaction (PPI) inhibitors towards binary interactors consisting of an intrinsically disordered epitope and a structured domain surface.     

Order out of Chaos

The current crisis in the world's fisheries indicates the need for a different management method than that now used by Western scientists, which regulates the quantity of fish taken. The authors propose a method called parametric management, which takes into account the complex, chaotic nature offish stocks and emphasizes preserving regular biological processes in the life cycle of fish by controlling how people fish. Supporting data come from 28 folk societies, the Maine lobster industry, and the authors' mathematical model of fish stocks.