Luminescence research and its relation to ultraweak cell radiation

The fundamental laws of photochemistry and the essential results of experimental research on ultraweak cell radiation are presented. By comparing all the facts it can be concluded that the phenomena discussed may arise from a variety of possible reactions and sources. Recombination reactions of certain radicals actually do release sufficient energy to generate UV-photons of the intensity under consideration. On the other hand, stimulated emission cannot be excluded in view of the distinct deviation of the radiation field from thermal equilibrium. There exist, however, various other candidates, such as direct emitters like flavins, indoles, porphyrins, carbonyl derivatives and aromatic compounds, and molecular oxygen and its various species, as well as collective molecular interactions, e.g. dimole or exciplex transitions, triplet-triplet annihilation, collective hydrolysis, electric field effects in membranes, etc. Careful biochemical and biophysical experiments are still necessary to find answers to all the questions that remain; not only individual problems have to be solved, but it is important to keep in mind the interrelationships between certain reactions.     

Structure,scale and emergence

In this paper I consider the structures that chemists and physicists attribute at the molecular scale to substances and materials of various kinds, and how they relate to structures and processes at other scales. I argue that the structure of a substance is the set of properties and relations which are preserved across all the conditions in which it can be said to exist. In short, structure is abstraction. On the basis of this view, and using concrete examples, I argue that structures, and therefore the chemical substances and other materials to which they are essential, are emergent. Firstly, structures themselves are scale-dependent because they can only exist within certain physical conditions, and a single substance may have different structures at different scales (of length, time and energy). Secondly, the distinctness of both substances and structures is a scale-dependent relationship: above a certain point, two distinct possibilities may become one. Thirdly, the necessary conditions for composition, for both substances and molecular species, are scale-dependent. To know whether a group of nuclei and electrons form a molecule it is not enough to consider energy alone: one also has to know about their environment and the lifetime over which the group robustly hangs together.     

Die Immunoelektrophorese in Agar-Gel

Summary An account is given of Immuno-electrophoresis, as it originated from a combination of electrophoresis in agar-jelly and the various experiences with antigen/antibody reactions in gels. The theoretical background is detailed as well as different techniques. The increased sensitivity has gained us new insight into the composition of body fluids. Finally the limitations are discussed as they are proper to all reactions which have an immuno-chemical basis.     

Regulatory aspects of low intensity photon emission

Photon emission from unicellular and multicellular organisms has been a subject of study for many decennia. In contrast to the well-known phenomenon of bioluminescence originating in luciferin-luciferase reactions, low intensity emission in the visible region of the electromagnetic spectrum has been found in almost every species studied so far. At present, the nomenclature of this phenomenon has not crystallized and it is referred to by a variety of names, such as mitogenetic radiation 29, dark luminescence 7, low-level chemiluminescence 20,36, and biophotons 57. Particular attention has been focussed on the relationship between photon emission and the regulation of various aspects of cellular metabolism, although in many cases quantitative data are still lacking. Throughout the history of this field of research the question of a functional biological role of the low intensity emission has been repeatedly raised; this is reflected, for instance, in the heterogeneity of the terms used to describe it. The discussion concerns the possible participation of photons of low intensity in intra- and intercellular communication. This paper reviews literature on the metabolic regulation of low intensity emission, as well as the regulation of photon emission initiated by external light. Furthermore, recent data are discussed with respect to a possible biocommunicative function of low intensity photon emission.     

Towards in vitro molecular diagnostics using nanostructures

Nanostructures appear to be promising for a number of applications in molecular diagnostics, mainly due to the increased surface-to-volume ratio they can offer, the very low limit of detection achievable, and the possibility to fabricate point-of-care diagnostic devices. In this paper, we review examples of the use of nanostructures as diagnostic tools that bring in marked improvements over prevalent classical assays. The focus is laid on the various sensing paradigms that possess the potential or have demonstrated the capability to replace or augment current analytical strategies. We start with a brief introduction of the various types of nanostructures and their physical properties that determine the transduction principle. This is followed by a concise collection of various functionalization protocols used to immobilize biomolecules on the nanostructure surface. The sensing paradigms are discussed in two contexts: the nanostructure acting as a label for detection, or the nanostructure acting as a support upon which the molecular recognition events take place. In order to be successful in the field of molecular diagnostics, it is important that the nanoanalytical tools be evaluated in the appropriate biological environment. The final section of the review compiles such examples, where the nanostructure-based diagnostic tools have been tested on realistic samples such as serum, demonstrating their analytical power even in the presence of complex matrix effects. The ability of nanodiagnostic tools to detect ultralow concentrations of one or more analytes coupled with portability and the use of low sample volumes is expected to have a broad impact in the field of molecular diagnostics.     

Atom transfer mechanisms in oxidation processes

The emphasis placed on electron transfer in connection with oxidation reactions has often resulted in these processes being considered as a group apart from the main class of chemical reactions. Although some oxidations, for example certain exchange reactions between ions in solution, can be reasonably described as electron transfer processes, there are very many other oxidations, whose mechanisms are much better described in the familiar terms of modern organic chemistry.The use of isotopes as tracers has shown, that many oxidations proceed with transfer of atoms or groups from oxidant to reductant andvice versa; the use of the kinetic isotope effect has shown that such transfer is seldom an incidental process, but is almost always a part of the slow step of the reaction. In this paper, oxidations involving the transfer of such species as oxygen atoms, hydride ions, hydrogen atoms, chlorine atoms, and hydroxyl radicals are discussed in terms of mechanism. An attempt is made to show that a graded series of mechanisms is possible ranging from what appear to be pure electron transfer processes at one end to certain atom transfer processes at the other. The latter group belong, in fact, in the familiar realm of ordinary chemical raactions, in which strong bonds are being broken and formed in the activated complex.Contribution from Department of Chemistry, University of British Columbia, Vancouver. — Presented at the Organic Chemistry Symposium of the Chemical Institute of Canada, Ottawa, Dec. 8–9, 1958.     

Platelets in defense against bacterial pathogens

Platelets interact with bacterial pathogens through a wide array of cellular and molecular mechanisms. The consequences of this interaction may significantly influence the balance between infection and immunity. On the one hand, recent data indicate that certain bacteria may be capable of exploiting these interactions to gain a virulence advantage. Indeed, certain bacterial pathogens appear to have evolved specific ways in which to subvert activated platelets. Hence, it is conceivable that some bacterial pathogens exploit platelet responses. On the other hand, platelets are now known to possess unambiguous structures and functions of host defense effector cells. Recent discoveries emphasize critical features enabling such functions, including expression of toll-like receptors that detect hallmark signals of bacterial infection, an array of microbicidal peptides, as well as other host defense molecules and functions. These concepts are consistent with increased risk and severity of bacterial infection as correlates of clinical abnormalities in platelet quantity and quality. In these respects, the molecular and cellular roles of platelets in host defense against bacterial pathogens are explored with attention on advances in platelet immunobiology.     

On conceptual issues in classical electrodynamics: Prospects and problems of an action-at-a-distance interpretation

Some conceptual issues in the foundations of classical electrodynamics concerning the interaction between particles and fields have recently received increased attention among philosophers of physics. After a brief review of the debate, I argue that there are essentially two incompatible solutions to these issues corresponding to F.A. Muller's distinction between the extension and the renormalization program. Neither of these solutions comes free of cost: the extension program is plagued with all problems related to extended elementary charges, the renormalization program works with point charges but trades in the notorious divergences of the field energies. The aim of this paper is to bring back into the discussion a third alternative, the action-at-a-distance program, which avoids both the riddles of extended elementary charges as well as the divergences although it admittedly has other problems. It will be discussed, why action-at-a-distance theories are actually not a far cry from particle–field theories, and I will argue that the main reasons for rejecting action-at-a-distance theories originate in certain metaphysical prejudices about locality and energy conservation. I will broadly suggest how these concepts could be adapted in order to allow for action at a distance.     

Theearly andlate processing of lysosomal enzymes: Proteolysis and compartmentation

Lysosomal enzymes are subjected to a number of modifications including carbohydrate restructuring and proteolytic maturation. Some of these reactions support lysosomal targeting, others are necessary for activation or keeping the enzyme inactive before being segregated, while still others may be adventitious. The non-segregated fraction of the enzyme is secreted and can be isolated from the medium. It is considered that the secreted lysosomal enzymes fulfill certain physiological and pathophysiological roles. By comparing the secreted and the intracellular enzymes it is possible to distinguish between the reactions that occur before and after the segregation. In this review the reactions that may influence the segregation are referred to as the early processing and those characteristic for the enzymes isolated from lysosomal compartments as the late processing. The early processing is characterized mainly by modifications of carbohydrate side chains. In the late processing, proteolytic fragmentation represents the most conspicuous changes. The review focuses on the compartmentation of the reactions and the proteolytic fragmentation of lysosomal enzyme precursors. While a plethora of proteolytic reactions are involved, our knowledge of the proteinases responsible for the particular maturation reactions remains very limited. The review points also to work with cells from patients affected with lysosomal storage disorders, which contributed to our understanding of the lysosomal apparatus.     

The early and late processing of lysosomal enzymes: proteolysis and compartmentation.

Lysosomal enzymes are subjected to a number of modifications including carbohydrate restructuring and proteolytic maturation. Some of these reactions support lysosomal targeting, others are necessary for activation or keeping the enzyme inactive before being segregated, while still others may be adventitious. The non-segregated fraction of the enzyme is secreted and can be isolated from the medium. It is considered that the secreted lysosomal enzymes fulfill certain physiological and pathophysiological roles. By comparing the secreted and the intracellular enzymes it is possible to distinguish between the reactions that occur before and after the segregation. In this review the reactions that may influence the segregation are referred to as the early processing and those characteristic for the enzymes isolated from lysosomal compartments as the late processing. The early processing is characterized mainly by modifications of carbohydrate side chains. In the late processing, proteolytic fragmentation represents the most conspicuous changes. The review focuses on the compartmentation of the reactions and the proteolytic fragmentation of lysosomal enzyme precursors. While a plethora of proteolytic reactions are involved, our knowledge of the proteinases responsible for the particular maturation reactions remains very limited. The review points also to work with cells from patients affected with lysosomal storage disorders, which contributed to our understanding of the lysosomal apparatus.     

Collective cell migration of epithelial and mesenchymal cells

Directional cell migration is required for proper embryogenesis, immunity, and healing, and its underpinning regulatory mechanisms are often hijacked during diseases such as chronic inflammations and cancer metastasis. Studies on migratory epithelial tissues have revealed that cells can move as a collective group with shared responsibilities. First thought to be restricted to proper epithelial cell types able to maintain stable cell–cell junctions, the field of collective cell migration is now widening to include cooperative behavior of mesenchymal cells. In this review, we give an overview of the mechanisms driving collective cell migration in epithelial tissues and discuss how mesenchymal cells can cooperate to behave as a collective in the absence of bona fide cell–cell adhesions.     

Molecular paleontology

Molecular paleontology, i.e., the recovery of DNA from ancient human, animal, and plant remains is an innovative research field that has received progressively more attention from the scientific community since the 1980s. In the last decade, the field was punctuated by claims which aroused great interest but eventually turned out to be fakes - the most famous being the sequence of dinosaur DNA later shown to be of human origin. At present, the discipline is characterized by some certainties and many doubts. We know, for example, that we have reasonable chances to recover authentic DNA from a mammoth carcass, while our chances are negligible (or nonexistent) in the case of a dynastic mummy from Egypt. On the other hand, though we are developing convincing models of DNA decay in bone, we are not yet able to predict whether a certain paleontological or archeological site will yield material amenable to DNA analysis. This article reviews some of the most important and promising investigations using molecular paleontology approaches, such as studies on the conservation of DNA in human bone, the quest for ancient DNA in permafrost-frozen fauna, the Tyrolean iceman, and the Neandertals. Received 5 April 2001; received after revision 5 July 2001; accepted 5 July 2001     

The impact of W. K. Röntgen's discovery on the use of internalizable sources of ionizing energy in diagnostic and therapeutic nuclear medicine

The early history of cathode rays, X-rays and a third kind of natural radiation from several minerals and atomic fission is described. In this way the fundamental concept of radioactivity, laws of decay and atomic models were developed. With artificial radioactive isotopes, new tailored radiopharmaceuticals could be introduced into metabolic research, medical diagnostics and therapy. Von Hevesy's concept of the dynamic state of body constituents led to examination of the locations and movements of labelled atoms and molecules as a function of time. That was the birth of nucler medicine. The principles and value at the molecular level of several specific tracer studies in research and diagnostic or therapeutic use are explained. Typically, diagnostic tests with tracer agents are non-invasive and have low radiation exposure. Competing with other diagnostic and therapeutic modalities, nuclear medicine is a speciality in its own right. But there are moves to classify it as a subspecialization of other organ-oriented clinical disciplines. That is a misunderstanding of the radiologist's role and does not answer the question: What is the best way of woking for the patient? New horizons in diagnostic modalities, biochemistry, immunology, imaging and the use of immunogenic therapeutic agents demand a continuous cooperation within interdisciplinary teams. That is as necessary with radiologic departments, participating in changed organizational structures, as with other clinical departments.     

Minisatellite instability and germline mutation

Tandem-repeat DNA actively turns over in the genome by a variety of poorly understood dynamic mechanisms. Minisatellites, a class of tandem repeats, have been shown to cause disease by influencing gene expression, modifying coding sequences within genes or generating fragile sites. There has been recent rapid progress towards understanding molecular turnover processes at human minisatellites. Instability at GC-rich minisatellites appears to involve distinct mutation processes operating in somatic and germline cells. In the germline, complex conversion-like events occur, probably during meiosis. Repeat turnover appears to be controlled by intense recombinational activity in DNA flanking the repeat array, suggesting that minisatellites might evolve as by-products of localised meiotic recombination in the human genome. In contrast, AT-rich minisatellites appear to evolve by intra-allelic processes such as replication slippage. Curiously, minisatellites in other organisms appear to be more stable than their human counterparts, suggesting species-specific differences in turnover processes. Some yeast models display human-like minisatellite turnover processes at meiosis. However, all attempts to transfer human germline instability to transgenic mice have failed. Finally, tandem repeat instability in various species appears to be extremely sensitive to environmental agents such as radiation via a mechanism which remains enigmatic.     

揭开世界性系统农牧渔业基因组研究的序幕

以基因组测序为先导的农牧渔业系统基因组学研究是一项需要国际间进行协同攻关和紧密合作的重大项目计划。这种以应用为目的的基础科学研究项目无论是对发达国家还是对发展中国家而言都是非常重要和必要的。然而，我们必须清醒地意识到，当人类基因组和其他许多同人类健康相关的基因组以及一些模式生物基因组已经或即将被测序时，重要的农作物、牲畜、水产品基因组所受到的重视还远远不够。虽然我们正面对诸如政策制订、资金申请、地方发展重点、研究团体共识及技术革新等多方面的问题和挑战，人们还是提出了许多有关大规模测序及其投资收益的倡议或计划。由于大规模测序即全基因组鸟枪法(Wh01e Genome Shotgun or WGS)所产生的序列草图能覆盖整个基因组95％至99％的区域，从基因组草图中识别的基因连带其他资源比如分子标记、大片段插入克隆和cDNA序列的知识，为农牧渔业和环境生物学提供了丰富的信息和大量的工具。一旦这项重大计划得以实施并取得成功，所有国家的分子生物学家、遗传学家、实验生物学家。无论富裕或贫穷，都将站在同一科学起点上，基础基因组学信息的又一次大爆发将使我们的生活和环境拥有一个更美好的未来。我们热切呼吁全世界的各个研究基金会，也呼吁各个国家和国际政府机构与组织共同支持这场伟大的项目计划。     

A historical review of the problem of mitogenetic radiation

The 'miracle of caryokinesis' was the starting point that stimulated Alexander G. Gurwitsch to carry out his famous 'mitogenetic' experiments in 1923. The results obtained confirmed his hypothesis of a weak radiation from cells, which is able to trigger the growth of other cells. Extensive experimental work within the first two decades after this discovery indicated that the problem of mitogenetic radiation is generally related to the biological significance of UV-radiation. Both 'energetic' and 'informational' aspects have to be considered, namely radiation effective in activating molecules, and that involved in arranging them into larger units. The molecular organization of biological structures is evidently governed by nonequilibrium conditions needing the uptake or emission of radiation. These concepts of A. G. Gurwitsch can be linked with modern approaches based on hypotheses of coherence in biology, 'synergetics' and 'dissipative structures'. However, the question of causal interrelationships between this part of non-equilibrium radiation and biological matter on different levels of evolution has to be solved now.     

DNA damage repair and transcription

Double-strand breaks arise frequently in the course of endogenous - normal and pathological - cellular DNA metabolism or can result from exogenous agents such as ionizing radiation. It is generally accepted that these lesions represent one of the most severe types of DNA damage with respect to preservation of genomic integrity. Therefore, cells have evolved complex mechanisms that include cell-cycle arrest, activation of various genes, including those associated with DNA repair, and in certain cases induction of the apoptotic pathway to respond to double-strand breaks. In this review we discuss recent progress in our understanding of cellular responses to DNA double-strand breaks. In addition to an analysis of the current paradigms of detection, signaling and repair, insights into the significance of chromatin remodeling in the double-strand break-response pathways are provided.     

On geometric objects,the non-existence of a gravitational stress-energy tensor,and the uniqueness of the Einstein field equation

The question of the existence of gravitational stress-energy in general relativity has exercised investigators in the field since the inception of the theory. Folklore has it that no adequate definition of a localized gravitational stress-energetic quantity can be given. Most arguments to that effect invoke one version or another of the Principle of Equivalence. I argue that not only are such arguments of necessity vague and hand-waving but, worse, are beside the point and do not address the heart of the issue. Based on a novel analysis of what it may mean for one tensor to depend in the proper way on another, which, en passant, provides a precise characterization of the idea of a “geometric object”, I prove that, under certain natural conditions, there can be no tensor whose interpretation could be that it represents gravitational stress-energy in general relativity. It follows that gravitational energy, such as it is in general relativity, is necessarily non-local. Along the way, I prove a result of some interest in own right about the structure of the associated jet bundles of the bundle of Lorentz metrics over spacetime. I conclude by showing that my results also imply that, under a few natural conditions, the Einstein field equation is the unique equation relating gravitational phenomena to spatiotemporal structure, and discuss how this relates to the non-localizability of gravitational stress-energy. The main theorem proven underlying all the arguments is considerably stronger than the standard result in the literature used for the same purposes (Lovelock's theorem of 1972): it holds in all dimensions (not only in four); it does not require an assumption about the differential order of the desired concomitant of the metric; and it has a more natural physical interpretation.