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.     

The consequences of the discovery by W. C. Röntgen for present-day medical physics and radiation protection

When the German physicist W. C. Röntgen discovered X-rays, which were named after him, he introduced a new development in medicine and biology: together with the discoveries of A. H. Becquerel and M. Curie, radiology with its diagnostic and therapeutic methods was made possible. The medical physicist has an important task to fulfill in modern radiotherapy, nuclear medicine and radiodiagnostics. The longtime interdisciplinary collaboration has won the international recognition of medical physics as a scientific discipline, a health care profession and a university subject. Several incidents, including contemporary ones, show that the efforts made towards radiation protection must remain an important domain of the specialist.     

In vivo imaging of therapy-induced anti-cancer immune responses in humans

Immunotherapy aims to re-engage and revitalize the immune system in the fight against cancer. Research over the past decades has shown that the relationship between the immune system and human cancer is complex, highly dynamic, and variable between individuals. Considering the complexity, enormous effort and costs involved in optimizing immunotherapeutic approaches, clinically applicable tools to monitor therapy-induced immune responses in vivo are most warranted. However, the development of such tools is complicated by the fact that a developing immune response encompasses several body compartments, e.g., peripheral tissues, lymph nodes, lymphatic and vascular systems, as well as the tumor site itself. Moreover, the cells that comprise the immune system are not static but constantly circulate through the vascular and lymphatic system. Molecular imaging is considered the favorite candidate to fulfill this task. The progress in imaging technologies and modalities has provided a versatile toolbox to address these issues. This review focuses on the detection of therapy-induced anticancer immune responses in vivo and provides a comprehensive overview of clinically available imaging techniques as well as perspectives on future developments. In the discussion, we will focus on issues that specifically relate to imaging of the immune system and we will discuss the strengths and limitations of the current clinical imaging techniques. The last section provides future directions that we envision to be crucial for further development.     

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.     

New imaging probes to track cell fate: reporter genes in stem cell research

Cell fate is a concept used to describe the differentiation and development of a cell in its organismal context over time. It is important in the field of regenerative medicine, where stem cell therapy holds much promise but is limited by our ability to assess its efficacy, which is mainly due to the inability to monitor what happens to the cells upon engraftment to the damaged tissue. Currently, several imaging modalities can be used to track cells in the clinical setting; however, they do not satisfy many of the criteria necessary to accurately assess several aspects of cell fate. In recent years, reporter genes have become a popular option for tracking transplanted cells, via various imaging modalities in small mammalian animal models. This review article examines the reporter gene strategies used in imaging modalities such as MRI, SPECT/PET, Optoacoustic and Bioluminescence Imaging. Strengths and limitations of the use of reporter genes in each modality are discussed.     

Between meaning culture and presence effects: contemporary biomedical objects as a challenge to museums

The acquisition and display of material artefacts is the raison d’être of museums. But what constitutes a museum artefact? Contemporary medicine (biomedicine) is increasingly producing artefacts that do not fit the traditional museological understanding of what constitutes a material, tangible artefact. Museums today are therefore caught in a paradox. On the one hand, medical science and technologies are having an increasing pervasive impact on the way contemporary life is lived and understood and is therefore a central part of the contemporary world. On the other hand, the objects involved in medical diagnostics and therapies are becoming increasingly invisible and intangible and therefore seem to have no role to play as artefacts in a museum context. Consequently, museums are at risk of becoming alienated from an increasingly important part of contemporary society. This essay elaborates the paradox by employing Gumbrecht’s (2004) distinction between ‘presence’ and ‘meaning’.     

Radiation physics

Summary A review is presented of the recent literature in the areas of physics which deal with radiation effects on man and animals. Some consideration is given to natural and artificial radiation sources such as cosmic rays, radon and high energy accelerators. The interaction of radiation with matter is treated if it is related to an energy deposition pattern relevant to biological effects. Dosimetry is also treated, with special emphasis on papers dealing with spatial dose distribution on a microscopic level, and radiobiological models relating the energy deposition pattern to biological effects are cited. New techniques in the medical application of radiation in diagnostics and therapy are briefly mentioned.     

Radiation physics

A review is presented of the recent literature in the areas of physics which deal with radiation effects on man and animals. Some consideration is given to natural and artificial radiation sources such as cosmic rays, radon and high energy accelerators. The interaction of radiation with matter is treated if it is related to an energy deposition pattern relevant to biological effects. Dosimetry is also treated, with special emphasis on papers dealing with spatial dose distribution on a microscopic level, and radiobiological models relating the energy deposition pattern to biological effects are cited. New techniques in the medical application of radiation in diagnostics and therapy are briefly mentioned.     

信息几何理论与应用研究进展

信息几何是在Riemann流形上采用现代微分几何方法来研究统计学问题的基础性、前沿性学科,被誉为是继Shannon开辟现代信息理论之后的又一新的理论变革,在信息科学与系统理论研究领域展现出了巨大的发展潜力．本文首先从参数化概率分布族的内蕴几何结构特征与信息的几何性质出发,精炼了信息几何的科学内涵,指出信息几何相比于经典统计学与信息论的理论优势与方法的革新．然后简要阐述了信息几何与微分几何的联系,综述了信息几何理论的发展历史与近20年来信息几何在神经网络、统计推断、通信编码、系统理论、物理学和医学成像等各领域应用的研究现状,归纳和总结了其中所体现的信息几何的基本原理和基本方法,并对信息几何的发展给予注记．特别地,对信息几何在信号处理领域中的应用成果进行了较全面的总结和概括,阐述了信息几何在信号检测、参数估计与滤波等方面的最新研究成果．最后,展望信息几何的发展前景,提出了信息几何在信号处理领域中的若干开放性问题．     

Multiple roles of class I HDACs in proliferation, differentiation, and development

Class I Histone deacetylases (HDACs) play a central role in controlling cell cycle regulation, cell differentiation, and tissue development. These enzymes exert their function by deacetylating histones and a growing number of non-histone proteins, thereby regulating gene expression and several other cellular processes. Class I HDACs comprise four members: HDAC1, 2, 3, and 8. Deletion and/or overexpression of these enzymes in mammalian systems has provided important insights about their functions and mechanisms of action which are reviewed here. In particular, unique as well as redundant functions have been identified in several paradigms. Studies with small molecule inhibitors of HDACs have demonstrated the medical relevance of these enzymes and their potential as therapeutic targets in cancer and other pathological conditions. Going forward, better understanding the specific role of individual HDACs in normal physiology as well as in pathological settings will be crucial to exploit this protein family as a useful therapeutic target in a range of diseases. Further dissection of the pathways they impinge on and of their targets, in chromatin or otherwise, will form important avenues of research for the future.     

Dynamics of the nuclear envelope at mitosis and during apoptosis

The nuclear envelope is a highly dynamic structure that reversibly disassembles and reforms at mitosis. The nuclear envelope also breaks down--irreversibly--during apoptosis, a process essential for development and tissue homeostasis. Analyses of fixed cells, time-lapse, imaging studies of live cells and the development of powerful cell-free extracts derived from gametes or mammalian somatic cells have provided insights on the fate of nuclear envelope proteins during mitosis and apoptosis, and on the mechanisms behind nuclear envelope modifications in these processes. In this review, we discuss evidence leading to our understanding of the dynamics of the nuclear envelope alterations at mitosis and during apoptosis. We also present novel imaging and genetic approaches to the study of nuclear envelope dynamics and function.     

A demonstration of the resolution of NMR imaging in biological systems

Summary A proton NMR imaging study of several fruit specimens demonstrates the integrity and resolution of this new imaging method.Acknowledgment. We thank Professor E. R. Andrew, Dr W. S. Moore and Miss C. Simaroj for their contributions. The work was supported by MRC grant G975-102.     

A demonstration of the resolution of NMR imaging in biological systems.

A proton NMR imaging study of several fruit specimens demonstrates the integrity and resolution of this new imaging method.     

ARARMA models for time series analysis and forecasting

Methods of time series forecasting are proposed which can be applied automatically. However, they are not rote formulae, since they are based on a flexible philosophy which can provide several models for consideration. In addition it provides diverse diagnostics for qualitatively and quantitatively estimating how well one can forecast a series. The models considered are called ARARMA models (or ARAR models) because the model fitted to a long memory time series (t) is based on sophisticated time series analysis of AR (or ARMA) schemes (short memory models) fitted to residuals Y(t) obtained by parsimonious‘best lag’non-stationary autoregression. Both long range and short range forecasts are provided by an ARARMA model Section 1 explains the philosophy of our approach to time series model identification. Sections 2 and 3 attempt to relate our approach to some standard approaches to forecasting; exponential smoothing methods are developed from the point of view of prediction theory (section 2) and extended (section 3). ARARMA models are introduced (section 4). Methods of ARARMA model fitting are outlined (sections 5,6). Since‘the proof of the pudding is in the eating’, the methods proposed are illustrated (section 7) using the classic example of international airline passengers.     

Sequential proteome alterations during genesis and progression of colon cancer

Changes in the proteome of colon mucosal cells accompany the transition from normal mucosa via adenoma and invasive cancer to metastatic disease. Samples from 15 patients with sporadic sigmoid cancers were analyzed. Proteins were separated by two-dimensional gel electrophoresis. Relative differences in expression levels between normal tissue, adenoma, carcinoma and metastasis were evaluated in both intra- and inter-patient comparisons. Up- and down-regulated proteins (<twofold) during development to cancer or metastasis were excised and submitted to peptide mass fingerprinting and MS/MS sequence analysis, facilitated by the use of a compact disc workstation. In total, 112 protein spots were found to be differentially regulated, of which 72 were determined as to protein identity, 46 being up-regulated toward the progression of cancer, and 26 down-regulated. Several of the identifications correlate with proteins of the cell cycle, cytoskeleton or metabolic pathways. The pattern changes now identified have the potential for design of marker panels for assistance in diagnostics and therapeutic strategies in colorectal cancer.Received 2 February 2004; received after revision 16 March 2004; accepted 18 March 2004     

Genetic studies of diseases

Functional imaging techniques such as positron and single-photon emission tomography exploit the relationship between neural activity, energy demand and cerebral blood flow to functionally map the brain. Despite the fact that neurobiological processes are not completely understood, several results have revealed the signals that trigger the metabolic and vascular changes accompanying variations in neural activity. Advances in this field have demonstrated that release of the major excitatory neurotransmitter glutamate initiates diverse signaling processes between neurons, astrocytes and blood perfusion, and that this signaling is crucial for the occurrence of brain imaging signals. Better understanding of the neural sites of energy consumption and the temporal correlation between energy demand, energy consumption and associated cerebrovascular hemodynamics gives novel insight into the potential of these imaging tools in the study of metabolic neurodegenerative disorders.     

Clostridial neurotoxins: structure-function led design of new therapeutics

The neurotoxins produced by various species of Clostridia are the causative agents of botulism and tetanus. The ability of the toxins, specifically those of the botulinum neurotoxin family, to disrupt neurotransmission has been exploited for use in several medical indications and now represents the therapeutic option of choice in a number of cases. Clostridial neurotoxins have been discovered to have a multi-domain structure that is shared between the various proteins of the family, and it has also been determined that each domain contributes a specific role to the holotoxin. The extensive use of recombinant expression approaches, along with solution of multiple crystallographic structures of individual domains, has enabled researchers to explore structurefunction relationships of the toxin domains more closely. These advances have facilitated a greater understanding of the potential use of individual domains for a wide variety of purposes, including the development of new therapeutics. Received 21 October 2005; received after revision 10 November 2005; accepted 16 November 2005     

多数据融合的医疗器械行业技术发展评估模型

为了能够更准确地把握医疗器械行业的发展趋势,根据医疗器械行业与科学技术的密切相关性,利用 D S证据理论的数据融合方法,建立了应用于医疗器械行业中评估科学技术的发展评估模型,并以“超声”技术在医疗器械行业中的发展进行了实例分析,获得了满意的效果,说明了所建模型的有效性和实用性     

Inhibitors of protein translocation across membranes of the secretory pathway: novel antimicrobial and anticancer agents

Proteins routed to the secretory pathway start their journey by being transported across biological membranes, such as the endoplasmic reticulum. The essential nature of this protein translocation process has led to the evolution of several factors that specifically target the translocon and block translocation. In this review, various translocation pathways are discussed together with known inhibitors of translocation. Properties of signal peptide-specific systems are highlighted for the development of new therapeutic and antimicrobial applications, as compounds can target signal peptides from either host cells or pathogens and thereby selectively prevent translocation of those specific proteins. Broad inhibition of translocation is also an interesting target for the development of new anticancer drugs because cancer cells heavily depend on efficient protein translocation into the endoplasmic reticulum to support their fast growth.