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Thanks to the progress in early diagnosis and treatment of cancer, the life expectancy of cancer patients has now increased. Patients are, therefore, more likely to experience their individual cancer pain as a chronic pain. As a consequence, long-term treatment of cancer-related pain and oncological therapy-related pain are a major need for all patients and a challenge to all healthcare professionals. Tapentadol is a centrally acting analgesic drug characterized by two synergistic mechanisms of action, since it acts at the µ-opioid receptor (MOR) and inhibits noradrenalin re-uptake (NRI). Therefore, tapentadol has been considered the first of a new class of drugs, MOR-NRI. Tapentadol has been tested in different populations of cancer patients (opioid-naive and -pretreated), such as those with pain of mixed etiology, patients with pain from hematological malignancies and patients experiencing pain conditions due to anticancer treatment. According to available evidence, tapentadol prolonged release was well tolerated and effective in cancer pain patients. In randomized, double-blind and active-controlled trials it proved non-inferior to standard opioids like morphine or oxycodone in the management of moderate-to-severe cancer pain, both in opioid-naive and in opioid-pretreated patients. The good analgesic efficacy may be partly due to the action of tapentadol on neuropathic pain components. Together with the low rate of gastrointestinal adverse effects and the overall favorable safety profile, tapentadol can be considered a good option in cancer pain patients, who can suffer frequently from nausea, vomiting, constipation or other events that further reduce their quality of life.

Magnetospirillum gryphiswaldense is a helix-shaped magnetotactic bacterium that synthesizes iron-oxide nanocrystals, which allow navigation along the geomagnetic field. The bacterium has already been thoroughly investigated at the molecular and cellular levels. However, the fundamental physical property enabling it to perform magnetotaxis, its magnetic moment, remains to be elucidated at the single cell level. We present a method based on magnetic tweezers; in combination with Stokesian dynamics and Boundary Integral Method calculations, this method allows the simultaneous measurement of the magnetic moments of multiple single bacteria. The method is demonstrated by quantifying the distribution of the individual magnetic moments of several hundred cells of M. gryphiswaldense. In contrast to other techniques for measuring the average magnetic moment of bacterial populations, our method accounts for the size and the helical shape of each individual cell. In addition, we determined the distribution of the saturation magnetic moments of the bacteria from electron microscopy data. Our results are in agreement with the known relative magnetization behavior of the bacteria. Our method can be combined with single cell imaging techniques and thus can address novel questions about the functions of components of the molecular magnetosome biosynthesis machinery and their correlation with the resulting magnetic moment.

Introduction. A historical overview is often quite useful in search for answers to some pressing issues. Learning from others can also help to cope with separate current problems. One of such problems encountered by modern Russian professional education is restoration and consolidation of its practice orientation through selection of an appropriate content and upbringing of youth in the course of pre-employment process. A considerable variety of material in this regard has been accumulated over the last several centuries in Germany. The aim of this paper was to analyse the cause-and-effect relationships of developmental priorities in the German professional pedagogy during the 18th – early 20th centuries.Methodology and research methods. System and comparative approaches were used as main methodological tools. The leading method was a comparative retrospective analysis, which allowed the authors to compare various scientific resources. In addition, the approaches of goal-setting and formalisation of expected results were applied. The content analysis and systematisation of documents and other historical and pedagogical resources were employed. In view of information extensiveness, the selection was compiled with the principle of necessity and sufficiency, i. e. reduction of excess data when maintaining the completeness of facts for continued use. Results and scientific novelty. The stages of formation and development of labour school were identified according to the ideas of the German scientists and the educational practice accepted in Germany during the considered historical period. The main directions of training through activity were characterised: philanthropinism, manualism, professionalism and activism. The influence of social and economic conditions on formation and transformation of various educational concepts was demonstrated, which constant despite everything was a combination of fundamental and applied components of vocational training. The continuity of pedagogical theory and practice of the past in the modern system of the German professional education was shown.Practical significance. The findings obtained by the Russian-German research team can be useful when developing and implementing flexible and adaptive differentiated curricula into modern vocational education in Russia. Введение. Исторический экскурс зачастую бывает весьма полезен при поиске ответов на злободневные вопросы. Изучение чужого опыта также может помочь справиться с отдельными актуальными проблемами. Одной из таких проблем, стоящих перед современным российским профессиональным образованием, является восстановление и закрепление его практикоориентированности путем отбора оптимального содержания воспитания молодежи в процессе подготовки к трудовой деятельности. Обширный материал в этом плане накоплен за несколько последних столетий в Германии. Цель статьи – выявление причинно-следственных связей смены приоритетов в процессе развития немецкой профессиональной педагогики на протяжении XVIII – начала XX в. Методология и методы. В качестве основного методологического инструментария были задействованы системный и компаративный подходы к решению исследовательских задач. Ведущим методом представленной в публикации работы был сравнительно-ретроспективный анализ, позволивший сопоставить различные научные источники информации. Кроме того, применялись методы целеполагания и формализации ожидаемых результатов; контент-анализ и систематизация документов и иной историко-педагогической информации, при отборе которой ввиду ее обширности соблюдался принцип необходимости и достаточности – сокращения избыточных сведений при сохранении полноты фактов для дальнейшего их использования. Результаты и научная новизна. Определены этапы становления и развития трудовой школы в соответствии с идеями, выдвигаемыми немецкими учеными, и образовательной практикой, принятой в Германии в рассматриваемый исторический период. Охарактеризованы основные направления обучения через деятельность: филантропизм, мануализм, профессионализм, активизм. Продемонстрировано влияние социально-экономических условий на формирование и трансформацию различных концепций воспитания и обучения, константой которых, несмотря ни на что, оставалось сочетание фундаментальной и прикладной составляющих профессиональной подготовки. Показана преемственность педагогической теории и практики с прошлым современной системы профессионального образования ФРГ. Практическая значимость. Выводы, полученные в результате предпринятого ретроспективного изыскания, осуществленного российско-германской группой исследователей, могут быть востребованы при разработке и внедрении гибких, адаптивных практикоориентированных образовательных программ в российском профессиональном образовании. Federal Institute for Development of Education German Federal Institute for Vocational Education Федеральный институт развития образования Федеральный институт профессионального образования ФРГ

Introduction. Nowadays, in Russia the system of interaction between educational institutions and enterprises-employers in training of specialists is being built again after more than a twenty-year period of dissociation. Sharing experiences with other countries on networking and strengthening of education relations with production is very useful for establishing this process. The aim of the publication is to present the results of the Russian-German cooperation in the field of preparation of the qualified pedagogical staff for the system of vocational education as one of the key conditions for ensuring the proper quality of vocational education. Methodology and research methods. The methods involve the methodology of comparative research; methods of collecting empirical information; conceptual and terminological analysis, interpretation, modeling, and problem method. Results. The approaches to preparation of pedagogical staff of the VET system in Germany and Russia are revealed and compared. Specifics of the German model are shown: existence of several skill levels of teachers of vocational education, distribution of zones of their responsibility, variability of providers of additional education, its market nature and minimum participation in its regulation of the state. Features of the modern Russian theory and training experience of instructors of vocational training are described. Despite the existing distinctions of systems of professional education of two countries, the similarity of the Russian and German methods of vocational education is observed. The conclusion is drawn on a community of requirements imposed in Germany and Russia to category of the workers who are carrying out staff training for manufacturing sectors. It is confirmed by the German experts on the basis of the analysis of the standard «Teacher of Vocational Education, Professional Education and Additional Professional Education». Also, the standard was checked and compared to AEVO (the regulatory base defining federal requirements to instructors-teachers in Germany). Scientific novelty consists in justification of modern model of training for VET teachers and trainers. The model provides implementation of variable modular curricula of additional vocational education for VET teachers and trainers. The most fruitful Russian and German experience is integrated; the international requirements and advanced technologies are considered when creating the model of training. Practical significance. Except the model of training for VET teachers and trainers, the education guidance «Methods of Vocational Education» is worked out. The education guidance summary is outlined in the present article. Введение. В России после более чем двадцатилетнего периода разобщенности между образовательными учреждениями и предприятиями -работодателями вновь начинает выстраиваться система их взаимодействия в подготовке специалистов. Для налаживания этого процесса весьма полезным является обмен опытом с другими странами по налаживанию и укреплению связей сферы образования с производством. Цель статьи состоит в том, чтобы представить результаты российско-германского сотрудничества в области обеспечения одного из ключевых условий качества профессионального образования - подготовки квалифицированных педагогических кадров для системы профессионального обучения. Методология и методы. В работе использовались методология сравнительного исследования; методы сбора эмпирической информации; понятийно-терминологический анализ, интерпретация, моделирование и проблемный метод. Результаты. Выявлены и сопоставлены подходы к подготовке педагогических кадров системы профессионального образования в ФРГ и России. Показана специфика немецкой модели: наличие нескольких уровней квалификации педагогов профессионального обучения, распределение зон их ответственности, вариативность провайдеров дополнительного образования, его рыночный характер и минимальное участие государства в его регулировании. Описаны особенности современной российской теории и практики подготовки мастеров производственного обучения. Отмечается, что, несмотря на существующие различия систем профессионального образования двух стран, прослеживается сходство отечественных и немецких методик профессионального обучения. Сделан вывод об общности требований, предъявляемых в Гер мании и России к категории работников, осуществляющих обучение персонала для производственного сектора. Это, в частности, подтверждено немецкими экспертами на основе анализа стандарта «Педагог профессионального обучения, профессионального образования и дополнительного профессионального образования» и сравнения его с AEVO - нормативной базой, определяющей федеральные требования к инструкторам-педагогам в ФРГ. Научная новизна работы состоит в обосновании современной модели подготовки мастеров производственного обучения и работников, осуществляющих обучение на производстве. Модель предусматривает реализацию вариативных модульных программ дополнительного профессионального образования. При создании данной модели был интегрирован наиболее плодотворный российский и немецкий опыт, учтены международные требования и передовые технологии. Практическая значимость. Кроме модели обучения мастеров-педагогов и производственных наставников, им в помощь разработано учебное пособие «Методика профессионального обучения», содержание которого частично и кратко изложено в статье.

Joseph Pergolizzi1, Eli Alon2, Ralf Baron3, Cesare Bonezzi4, Jan Dobrogowski5, Rafael Gálvez6, Troels Jensen7, Hans-Georg Kress8, Marco AE Marcus9, Bart Morlion10, Serge Perrot11, Rolf-Detlef Treede121Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA; 2Universitätsspital Zurich, Switzerland; 3Universitätsklinikum Schleswig-Holstein, Kiel, Germany; 4Fondazione Salvatore Maugeri, Pavia, Italy; 5Zaklad Badania i Leczenia Bólu, Kraków, Poland; 6Hospital Universitario Virgen de las Nieves, Granada, Spain; 7Aarhus University, Denmark; 8Medical University of Vienna, Austria; 9Maastricht University Medical Center and University of Muenster, Maastricht, The Netherlands; 10University Hospitals Leuven, Belgium; 11Hôpital Dieu, Paris, France; 12Ruprecht-Karls-University, Heidelberg, GermanyAbstract: Chronic pain affects approximately 1 in 5 people in Europe, and around half of sufferers receive inadequate pain management. The most common location is the lower back. Pharmacological treatment of this condition is challenging because of the range of causative mechanisms and the difficulty of balancing analgesic efficacy and tolerability. An international panel of clinical pain specialists met in September, 2009, to discuss the treatment of chronic low back pain, and to review preclinical and clinical data relating to the new analgesic, tapentadol. A lack of consensus exists on the best treatment for low back pain. The range of regularly prescribed pharmacological agents extends from nonopioids (paracetamol, NSAIDs, and COX-2 inhibitors) to opioids, antidepressants and anticonvulsants. Pain relief may be compromised, however, by an undetected neuropathic component or intolerable side effects. Treatment is potentially life-long and effective analgesics are urgently needed, with demonstrable long-term safety. Combining separate agents with different mechanisms of action could overcome the limitations of present pharmacological therapy, but clinical evidence for this approach is currently lacking. Tapentadol combines µ-opioid agonism with noradrenaline reuptake inhibition in a single molecule. There is strong evidence of synergistic antinociception between these two mechanisms of action. In preclinical and clinical testing, tapentadol has shown efficacy against both nociceptive and neuropathic pain. Preclinical data indicate that tapentadol’s µ-opioid agonism makes a greater contribution to analgesia in acute pain, while noradrenaline reuptake inhibition makes a greater contribution in chronic neuropathic pain models. Tapentadol also produces fewer adverse events than oxycodone at equianalgesic doses, and thus may have a ‘µ-sparing effect’. Current evidence indicates that tapentadol’s efficacy/tolerability ratio may be better than those of classical opioids. However, further research is needed to establish its role in pain management.Keywords: chronic low back pain, neurophysiological changes, neuropathic component, multimechanistic approach, efficacy/side effect ratio, tapentadol

The purpose of authors – the colleagues cooperating within the Russian-German working group on vocational education – is to determine features of the German dual system of vocational education and training (VET) which make it effective and popular not only in Germany, but also in the world. Methods. In the presented article the methodology of comparative research on the basis of the analysis of results of activity of Slovakia, Italy, South Korea, Russia and other countries on reforming of VET system on the basis of experience of Germany is used. Methods of collecting empirical information on the projects started in the specified countries, methods of the conceptual and terminological analysis, interpretation and modeling, a problem method are chosen. Results. Specifics of the German dual system are revealed; the generalized model of dual VET is constructed; features of approaches of the different countries to use positive experience of Germany for development of its own VET systems are characterized.Scientific novelty. The authors point out the consecutive justification of the conditions necessary for quality vocational education in modern market economy relying on results of the comparative analysis of reforming processes of VET systems in different countries. Practical significance. Need of public-private partnership as bases of quality of personnel preparation and ensuring economic competitiveness of the countries is shown and concrete ways of creation of such partnership in a number of the Russian regions are described. The experience presented above can be used throughout the Russian Federation Целью работы авторов – коллег, сотрудничающих в рамках Российско-Германской рабочей группы по профессиональному образованию – было определение особенностей немецкой дуальной системы профессионального образования и обучения, которые делают ее эффективной и популярной не только в Германии, но и в мире. Методология и методы. В ходе работы была задействована методология сравнительного исследования на основе анализа результатов деятельности Словакии, Италии, Южной Кореи, России и других стран по реформированию системы профессионального образования на основе опыта ФРГ. Использовались методы сбора эмпирической информации о проектах, запущенных в указанных странах; методы понятийно-терминологического анализа, интерпретации и моделирования, проблемный метод. Результаты. Выявлена специфика немецкой дуальной системы, построена обобщенная модель дуального профессионального образования и обучения, охарактеризованы особенности подходов разных стран к адаптации позитивного опыта Германии для развития собственных систем профессионального образования. Научная новизна работы состоит в последовательном обосновании условий, необходимых для качественного профессионального образования в современной ситуации рыночной экономики. С опорой на результаты сравнительного анализа показаны тенденции реформирования систем профессионального образования разных стран. Практическая значимость. Подтверждена необходимость государственно-частного партнерства как основы качества подготовки рабочих кадров и обеспечения экономической конкурентоспособности стран. Описаны конкретные пути создания такого партнерства в ряде российских регионов, чей опыт может быть распространен на всю территорию Российской Федерации.

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The mechanics of the actin cytoskeleton have a central role in the regulation of cells and tissues, but the details of how molecular sensors recognize deformations and forces are elusive. By performing cytoskeleton laser nanosurgery in cultured epithelial cells and fibroblasts, we show that the retraction of stress fibers (SFs) is restricted to the proximity of the cut and that new adhesions form at the retracting end. This suggests that SFs are attached to the substrate. A new computational model for SFs confirms this hypothesis and predicts the distribution and propagation of contractile forces along the SF. We then analyzed the dynamics of zyxin, a focal adhesion protein present in SFs. Fluorescent redistribution after laser nanosurgery and drug treatment shows a high correlation between the experimentally measured localization of zyxin and the computed localization of forces along SFs. Correlative electron microscopy reveals that zyxin is recruited very fast to intermediate substrate anchor points that are highly tensed upon SF release. A similar acute localization response is found if SFs are mechanically perturbed with the cantilever of an atomic force microscope. If actin bundles are cut by nanosurgery in living Drosophila egg chambers, we also find that zyxin redistribution dynamics correlate to force propagation and that zyxin relocates at tensed SF anchor points, demonstrating that these processes also occur in living organisms. In summary, our quantitative analysis shows that force and protein localization are closely correlated in stress fibers, suggesting a very direct force-sensing mechanism along actin bundles.

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Genes from two Drosophila virilis intermoult puffs were isolated by microcloning. From puff 16A on the X-chromosome a 2.9 kb DNA fragment was obtained, which hybridizes with three transcripts. Two of them represent the mRNAs for larval glue proteins. They are found in different abundancies in third larval instar salivary glands, but also in minor amounts in midgut and in fat body. In puff 55E on chromosome III two genes were identified. They are transcribed exclusively in salivary glands during all three larval instars. Therefore, their products must be related to another glandspecific function, which is sustained throughout larval fife.

Phagocytosis, which is a central cellular mechanism in the mammalian immune system, was so far - in the context of cell-biological studies - mainly investigated by conventional light and electron microscopies. However, the mechanical properties of this process, like the forces and energies involved were barely known up to now. Here, optical tweezers-based microscopy in combination with coated beads as bacterial model system was applied to investigate the mechanical properties of phagocytosis. The binding, the uptake into the cell and the intracellular transport of single optically trapped beads was induced by the optical trap and measured in 3D with nanometer precision by an interferometric tracking technique. Thereby, a novel cellular behaviour was discovered: A few seconds after binding, filopodia and ruffles retracted and pulled the bound beads towards the cell. The observation of discrete F-actin dependent 33-nanometer steps during retraction led to the hypothesis that a processive myosin motor plays an important role in the retraction. Force-velocity measurements revealed the mechanical properties of this putative motor. A model for the force-dependent motor kinetics confirming these results was developed. In order to perform these measurements, the microscope’s optical trapping and tracking properties were significantly improved and shown to be in very good agreement with theoretical predictions based on Fourieroptics and extendedMie-scattering theory.

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Der Einsatz von Visualisierungstechniken im Ingenieurbereich nimmt in dem Masse zu, wie Produktdaten in digitaler Form vorliegen und zur Visualisierung verwendet werden koennen. Mit der heute zur Verfuegung stehenden Hard- und Software wird ein interaktives Handhaben der Datensaetze in Echtzeit moeglich.Eine Kombination von realistischen und symbolischen Darstellungen erlaubt es, semantische Informationen der Produkte zu visualisieren und interaktiv zu bearbeiten. Diese Techniken koennen so zu Ergonomieuntersuchungen, Ein- und Ausbausimulationen, Praesentationen von Designmodellen oder zur Visualisierungvon Simulationsergebnissen eingesetzt werden. Der folgende Artikel gibt eine Uebersicht ueber Konzepte. Hard- und Softwarekomponenten, sowie eine Auswahl von Anwendungsfaellen fuer das Gebiet Visual Engineering.

Mit dem HP Shared 3D Viewer wird Konstruktions- und Entwicklungsabteilungen in den Bereichen Maschinen- und Anlagenbau, sowie Automobilbau und Luftfahrttechnik eine Anwendung zur Verfuegung gestellt, die den Informationsfluss bei der Produktentwicklung effizienter gestaltet. Da heutzutage Produkte zunehmend von oertlich verteilten Arbeitsgruppen entworfen werden, fuehrt dies zu einem deutlich erhoehten Abstimmungs- und Kommunikationsbedarf. Hier realisiert der HP Shared 3D Viewer Funktionalitaeten, die sowohl synchrone Kommunikation in einer Telekonferenz als auch asynchrone Kommentierung von Entwuerfen im off-line Betrieb ermoeglichen. Der HP Shared 3D Viewer wurde von Hewlett-Packard und dem Fraunhofer- Institut fuer Graphische Datenverarbeitung, Darmstadt in enger Kooperation entwickelt und wird seit September als Produkt von HP vertrieben.

The ability to rapidly prototype a proposed design is becoming a key contributor towards fulfilling the business requirements embodied in a short time-to-market, in cost-effective and high quality manufacturing, and in easy support and maintenance. Reorganizing the design and development process along the lines implied by the concept, Concurrent Engineering, means that advanced information technologies must be taken advantage of. However, most of taday's generic, commercial, off-the-shelf technologies have to be extended and adapted to the needs of the product development process. The integration of existing technologies in CAD modelling, design, analysis, simulation networked cooperation, and virtual reality leads to a distributed desktop-environment which provides the basis to take the greatest advantage of the Virtual Prototyping technique.

Mit dem HP Shared 3D Viewer wird Konstruktions- und Entwicklungsabteilungen in den Bereichen Maschinen- und Anlagenbau, sowie Automobilbau und Luftfahrttechnik eine Anwendung zur Verfügung gestellt, die den Informationsfluss bei der Produktentwicklung effizeinter gestaltet. Da heutzutage Produkte zunehmend von oertlich verteilten Arbeitsgruppen entworfen werden, führt dies zu einem deutlich erhoehten Abstimmungs- und Kommunikationsbedarf. Hier realisiert der HP Shared 3D Viewer Funktionalitaeten, die sowohl synchrone Kommunikation in einer Telekonferenz als auch asynchrone Kommentierung von Entwürfen im off-line Betrieb ermoeglichen.

CoConut (Computer Support for Concurrent Design using STEP) ist eine integrierte, verteilte Systemumgebung, die am Fraunhofer-Institut fuer Graphische Datenverarbeitung, Darmstadt entwickelt wurde. Sie erlaubt zeitgleiches und zeitversetztes Arbeiten mehrerer Konstrukteure am gleichen Produkt innerhalb einer oertlich verteilten Arbeitsgruppe. Das System verbessert einerseits die Kommunikation und die Kooperation zwischen Konstrukteuren und Projektverantwortlichen und gewaehrleistet andererseits die Konsistenz der zu bearbeitenden Daten durch eine system unabhaengige STEP-basierte Datenhaltung.