Some personal and historical notes on the utility of deep-etch electron microscopy for making cell structure/function correlations

This brief essay talks up the advantages of metal replicas for electron microscopy and explains why they are still the best way to image frozen cells in the electron microscope. Then it explains our approach to freezing, namely the Van Harreveld trick of “slamming” living cells onto a supercold block of metal sprayed with liquid helium at −269ºC, and further talks up this slamming over the alternative of high-pressure freezing, which is much trickier but enjoys greater favor at the moment. This leads me to bemoan the fact that there are not more young investigators today who want to get their hands on electron microscopes and use our approach to get the most “true to life” views of cells out of them with a minimum of hassle. Finally, it ends with a few perspectives on my own career and concludes that, personally, I'm permanently stuck with the view of the “founding fathers” that cell ultrastructure will ultimately display and explain all of cell function, or as Palade said in his Nobel lecture,electron micrographs are “irresistible and half transparent … their meaning buried under only a few years of work,” and “reasonable working hypotheses are already suggested by the ultrastructural organization itself.

Recent financial changes in Western Germany

Economic conditions - West Germany ; Finance

Vaults. III. Vault ribonucleoprotein particles open into flower-like structures with octagonal symmetry.

The structure of rat liver vault ribonucleoprotein particles was examined using several different staining techniques in conjunction with EM and digestion with hydrolytic enzymes. Quantitative scanning transmission EM demonstrates that each vault particle has a total mass of 12.9 +/- 1 MD and contains two centers of mass, suggesting that each vault particle is a dimer. Freeze-etch reveals that each vault opens into delicate flower-like structures, in which eight rectangular petals are joined to a central ring, each by a thin hook. Vaults examined by negative stain and conventional transmission EM (CTEM) also reveal the flower-like structure. Trypsin treatment of vaults resulted exclusively in cleavage of the major vault protein (p104) and concurrently alters their structure as revealed by negative stain/CTEM, consistent with a localization of p104 to the flower petals. We propose a structural model that predicts the stoichiometry of vault proteins and RNA, defines vault dimer-monomer interactions, and describes two possible modes for unfolding of vaults into flowers. These highly dynamic structural variations are likely to play a role in vault function

THE INTERNATIONAL CAPITAL MOVEMENT AS A FACTOR OF INFLUENCE ON INNOVATIVE DEVELOPMENT TENDENCY OF UKRAINE’S ECONOMY AND ITS INTEGRATION INTO THE WORLD ECONOMY

The article represents the research results concerning Ukraine’s solving strategic tasks to develop the financial mechanism of regulating the international capital movement and strengthening its positive effect on Ukraine’s economy development tendencies and innovative renewal of its domestic enterprises.The research results regarding Ukraine’s solving the strategic task of financial mechanisms of regulating the international capital movement and strengthening its positive effect on Ukraine’s economic development and innovative renewal of its economy are considered

Britain and the origins and future of the European defence and security mechanism

Throughout the second half of the twentieth century, the UK played a key role in the creation and development of a flexible and sustainable mechanism for European defence and security. Beatrice Heuser reviews the history of this engagement, and argues that changes in the UK’s institutional relationship with European partners should not be allowed to undermine the overarching principles of defence cooperation. Lessons learnt from history can be wrong or irrelevant, but one lesson that to a student of international relations seems both right and relevant appears to have been forgotten: that Britain’s security depends on a peaceful Europe; that Europe’s stability is enhanced by a firm British commitment to the defence of democratic states in Europe; and that the fine skills of British officials have been essential in overcoming many a crisis not only in transatlantic relations, but also in intra-European relations. Yet, today, Europe’s carefully crafted defence mechanism, engineered above all by Britain, is crumbling. This mechanism and the rules to guide its employment took decades to construct, and Britain was one of the leading powers in initiating, amending and then fine-tuning it. In key periods, this was achieved along with France; in others mainly alongside the US and West Germany. It was a mechanism that allowed for dynamism, elasticity and perpetual adjustments to ever-new events, which had to be accommodated without undermining the foundations of the entire structure. The British leaders and officials involved drew on centuries of failed experiments with alternative structures, all of which were eventually unable to keep the British Isles out of the two world wars, resulting in unprecedented numbers of casualties, damage and suffering. The mechanism, designed as much as cobbled together in ad hoc salvage operations by British politicians and defence planners, was at once robust and flexible, allowing it to weather a series of crises. But it relied and still relies crucially on Britain as the central lynchpin keeping the construct together. The British withdrawal from the EU risks removing this central lynchpin, upon which the entire construct may come apart

The Compressed Baryonic Matter Experiment at FAIR: Progress with feasibility studies and detector developments

The Compressed Baryonic Matter (CBM) experiment is being planned at the international research center FAIR, under realization next to the GSI laboratory in Darmstadt, Germany. Its physics programme addresses the QCD phase diagram in the region of highest net baryon densities. Of particular interest are the expected first order phase transition from partonic to hadronic matter, ending in a critical point, and modifications of hadron properties in the dense medium as a signal of chiral symmetry restoration. Laid out as a fixed-target experiment at the heavy-ion synchrotrons SIS-100/300, the detector will record both proton-nucleus and nucleus-nucleus collisions at beam energies between 10 and 45$A$ GeV. Hadronic, leptonic and photonic observables have to be measured with large acceptance. The interaction rates will reach 10 MHz to measure extremely rare probes like charm near threshold. Two versions of the experiment are being studied, optimized for either electron-hadron or muon identification, combined with silicon detector based charged-particle tracking and micro-vertex detection. The CBM physics requires the development of novel detector sytems, trigger and data acquisition concepts as well as innovative real-time reconstruction techniques. Progress with feasibility studies of the CBM experiment and the development of its detector systems are reported.Comment: 4 pages, 3 figures - FINAL - To appear in the conference proceedings for Quark Matter 2009, March 30 - April 4, Knoxville, Tennesse

Protease effects on the structure of acetylcholine receptor membranes from Torpedo californica.

Protease digestion of acetylcholine receptor-rich membranes derived from Torpedo californica electroplaques by homogenization and isopycnic centrifugation results in degradation of all receptor subunits without any significant effect on the appearance in electron micrographs, the toxin binding ability, or the sedimentation value of the receptor molecule. Such treatment does produce dramatic changes in the morphology of the normally 0.5- to 2-microns-diameter spherical vesicles when observed by either negative-stain or freeze-fracture electron microscopy. Removal of peripheral, apparently nonreceptor polypeptides by alkali stripping (Neubig et al. 1979, Proc. Natl. Acad. Sci. U. S. A. 76:690-694) results in increased sensitivity of the acetylcholine receptor membranes to the protease trypsin as indicated by SDS gel electrophoretic patterns and by the extent of morphologic change observed in vesicle structure. Trypsin digestion of alkali-stripped receptor membranes results in a limit degradation pattern of all four receptor subunits, whereupon all the vesicles undergo the morphological transformation to minivesicles. The protein-induced morphological transformation and the limit digestion pattern of receptor membranes are unaffected by whether the membranes are prepared so as to preserve the receptor as a disulfide bridged dimer, or prepared so as to generate monomeric receptor

On the Machine Learning Techniques for Side-channel Analysis

Side-channel attacks represent one of the most powerful category of attacks on cryptographic devices with profiled attacks in a prominent place as the most powerful among them. Indeed, for instance, template attack is a well-known real-world attack that is also the most powerful attack from the information theoretic perspective. On the other hand, machine learning techniques have proven their quality in a numerous applications where one is definitely side-channel analysis, but they come with a price. Selecting the appropriate algorithm as well as the parameters can sometimes be a difficult and time consuming task. Nevertheless, the results obtained until now justify such an effort. However, a large part of those results use simplification of the data relation from the one perspective and extremely powerful machine learning techniques from the other side. In this paper, we concentrate first on the tuning part, which we show to be of extreme importance. Furthermore, since tuning represents a task that is time demanding, we discuss how to use hyperheuristics to obtain good results in a relatively short amount of time. Next, we provide an extensive comparison between various machine learning techniques spanning from extremely simple ones ( even without any parameters to tune), up to methods where previous experience is a must if one wants to obtain competitive results. To support our claims, we give extensive experimental results and discuss the necessary conditions to conduct a proper machine learning analysis. Besides the machine learning algorithms' results, we give results obtained with the template attack. Finally, we investigate the influence of the feature (in)dependence in datasets with varying amount of noise as well as the influence of feature noise and classification noise. In order to strengthen our findings, we also discuss provable machine learning algorithms, i.e., PAC learning algorithms