Protein transduction: A novel tool for tissue regeneration

Tissue regeneration in humans is limited and excludes vitals organs like heart and brain. Transformation experiments with oncogenes like T antigen have shown that retrodifferentiation of the respective cells is possible but hard to control. To bypass the risk of cancer formation a protein therapy approach has been developed. The transient delivery of proteins rather than genes could still induce terminallydifferentiated cells to reenter the cell cycle. This approach takes advantage of proteintransducing domains that mediate the transfer of cargo proteins into cells. The goal of this brief review is to outline the basics of protein transduction and to discuss potential applications for tissue regeneration

Recruitment kinetics of DNA repair proteins Mdc1 and Rad52 but not 53BP1 depend on damage complexity.

The recruitment kinetics of double-strand break (DSB) signaling and repair proteins Mdc1, 53BP1 and Rad52 into radiation-induced foci was studied by live-cell fluorescence microscopy after ion microirradiation. To investigate the influence of damage density and complexity on recruitment kinetics, which cannot be done by UV laser irradiation used in former studies, we utilized 43 MeV carbon ions with high linear energy transfer per ion (LET = 370 keV/µm) to create a large fraction of clustered DSBs, thus forming complex DNA damage, and 20 MeV protons with low LET (LET = 2.6 keV/µm) to create mainly isolated DSBs. Kinetics for all three proteins was characterized by a time lag period T(0) after irradiation, during which no foci are formed. Subsequently, the proteins accumulate into foci with characteristic mean recruitment times τ(1). Mdc1 accumulates faster (T(0) = 17 ± 2 s, τ(1) = 98 ± 11 s) than 53BP1 (T(0) = 77 ± 7 s, τ(1) = 310 ± 60 s) after high LET irradiation. However, recruitment of Mdc1 slows down (T(0) = 73 ± 16 s, τ(1) = 1050 ± 270 s) after low LET irradiation. The recruitment kinetics of Rad52 is slower than that of Mdc1, but exhibits the same dependence on LET. In contrast, the mean recruitment time τ(1) of 53BP1 remains almost constant when varying LET. Comparison to literature data on Mdc1 recruitment after UV laser irradiation shows that this rather resembles recruitment after high than low LET ionizing radiation. So this work shows that damage quality has a large influence on repair processes and has to be considered when comparing different studies

Paleogeography of the Upper Rhine Graben (URG) and the Swiss Molasse Basin (SMB) from Eocene to Pliocene

Twenty paleogeographic maps are presented for Middle Eocene (Lutetian) to Late Pliocene times according to the stratigraphical data given in the companion paper by Berger et al. this volume. Following a first lacustrine-continental sedimentation during the Middle Eocene, two and locally three Rupelian transgressive events were identified with the first corresponding with the Early Rupelian Middle Pechelbronn beds and the second and third with the Late Rupelian ≪ Serie Grise ≫ (Fischschiefer and equivalents). During the Early Rupelian (Middle Pechelbronn beds), a connection between North Sea and URG is clearly demonstrated, but a general connection between North Sea, URG and Paratethys, via the Alpine sea, is proposed, but not proved, during the late Rupelian. Whereas in the southern URG, a major hiatus spans Early Aquitanian to Pliocene times, Early and Middle Miocene marine, brackish and freshwater facies occur in the northern URG and in the Molasse Basin (OMM, OSM); however, no marine connections between these basins could be demonstrated during this time. After the deposition of the molasse series, a very complex drainage pattern developed during the Late Miocene and Pliocene, with a clear connection to the Bresse Graben during the Piacenzian (Sundgau gravels). During the Late Miocene, Pliocene and Quaternary sedimentation persisted in the northern URG with hardly any interruptions. The present drainage pattern of the Rhine river (from Alpine area to the lower Rhine Embayment) was not established before the Early Pleistocen

Reducing Internal Electronic Noise in Electronic Devices

This publication describes systems and techniques to reduce internal electronic noise in electronic devices. In aspects, an electronic device includes one or more microphones that are mounted to a surface of an internal structure and a fastener assembly having a screw, an isolation bracket, and a washer. The washer can be utilized at an interface between at least two hardware components in the electronic device, such as the screw, the isolation bracket, and/or the structure on which the one or more microphones are mounted. The washer can reduce electronic noises (“e-noise”) and vibrations commonly found in electronic devices and can be used in devices with electromagnetic (EM) coupling issues

Tectono-sedimentary evolution of the northern Upper Rhine Graben (Germany), with special regard to the early syn-rift stage

• The present study focuses on the tectono-sedimentary interactions during the Cenozoic syn-rift stage of the northern Upper Rhine Graben. A special regard is given to the early syn-rift phase. The analysis is based on reflection seismic and well log information, which were generously made available by the German oil industry. The study method is a combination of the sedimentary models for extensional basins (Gawthorpe et al., 1994; Howell & Flint, 1996) and the base-level sequence stratigraphy (Cross & Lessenger, 1998). This method has proved to be a reliable tool for the structurally controlled settings of the northern Upper Rhine Graben. 1) Overall interpretation of the Cenozoic evolution • A large-scale interbasin transfer zone subdivided the northern Upper Rhine Graben into a southern and a northern halfgraben (sub-basin). The sub-basins have opposing tilt directions and their sedimentary fill is asymmetric. The transfer zone and the sub-basins are subdivided into fault blocks, which influenced sedimentation at subordinate scale. • The sediments of late Eocene to early Miocene age were classified into four large-scale base-level cycles. These reflect the variation of accommodation space and sediment supply with time. The base-level cycles are compared with the subsidence curves, calculated for a well in the northern Upper Rhine Graben, and with the regional variations in relative sea-level (Hardenbol et al., 1998). The Cenozoic large-scale base-level cycles of the northern Upper Rhine Graben were generated by the interplay between the tectonic activity of the graben and the major tectono-eustatic events recorded in several European Basins. 2) The early syn-rift depositional history • The early syn-rift succession (late Priabonian to early Rupelian) includes the Eocene Clay (where deposited), the Pechelbronn Beds, and the Rupelian Clay. This succession was deposited on tilt-blocks/halfgrabens bounded by growth faults. The halfgraben fill is wedge-shaped, and was generated during fault activity and block rotation. • The interbasin transfer zone was already active during the early syn-rift stage. It created an axial depositional gradient, dipping into the southern sub-basin, and represented a barrier between the two sub-basins. At subordinate scale, tilt-block/halfgrabens produced minor depocentres and depositional gradients. A low-displacement segment of the western border fault created a sediment input point, as drainage systems entered the graben through it. These structural features influenced accommodation space and sediment supply at different scales. • The early syn-rift succession was classified into two large-scale cycles (C-I-1 and C-I-2). The C-I-1 cycle is asymmetric, and contains the Lower Pechelbronn Beds and the lower part of the Middle Pechelbronn Beds. The C-I-2 cycle is symmetric and is composed of the upper part of the Middle Pechelbronn Beds, the Upper Pechelbronn Beds and the lower part of the Rupelian Clay. The characteristics of these base-level cycles (the ratio between accommodation space to sediment supply) varied as a function of the position within the tectonic framework of the graben. Even though the large-scale base-level cycles were probably influenced by regional variations in relative sea-level (affecting several European basins), the distribution of depositional systems and the palaeogeographic settings of the northern Upper Rhine Graben were controlled by the local syn-sedimentary tectonic structures

Autonome Shuttlebusse als Ergänzung zum ÖPNV in der Anbindung des suburbanen Raumes: Empirische Entwicklung eines Kriteriensystems zur Bewertung von Mobilitätskonzepten im öffentlichen Verkehr am Beispiel eines autonomen Shuttlebusses

Mit der vorliegenden Arbeit wurde ein systemischer Ansatz zur multi-kriterialen Bewertung von Mobilitätskonzepten im frühen Entwicklungsstadium konzeptioniert. Das aus 20 Kriterien bestehende Bewertungssystem ermöglicht dabei sowohl eine betriebswirtschaftliche als auch eine volkswirtschaftliche Betrachtungsebene. Um dies zu erreichen, galt es ausgewählte Kriterien zunächst auf ihre Integrationsfähigkeit hin zu überprüfen, da das Kriteriensystem unter anderem ohne Gesamtnetzzusammenhang auskommen muss. Im Folgenden wurden die gefilterten Kriterien soweit möglich monetarisiert und prototypisch abgetestet. Konzeptionell lehnt sich die Bewertungslogik an Vorgehensweisen von etablierten Nutzen-Kosten-Analysen im öffentlichen Verkehr an. Die definierten Kriterien sind indes zu gleichen Teilen den übergeordneten Zielstellungen „Erhöhung der Wirtschaftlichkeit“, der „Erhöhung der Umweltverträglichkeit“ sowie der „Verbesserung der Angebotsqualität“ des ÖPNV-Angebots zugeteilt. Die Evaluierung erfolgt durch einen Vergleich eines ausgewählten Plan-Falles mit zwei weiteren Referenz-Fällen. Im Rahmen dieser Forschungsarbeit wurde dabei ein autonomer Shuttlebus herangezogen, der durch die Deutsche Bahn im bayerischen Kurort Bad Birnbach betrieben wird. Als Referenzfälle wurden zum einen ein weit verbreiteter Niederflurbus sowie ein handelsüblicher Kleinbus ausgewählt. Durch die prototypische Anwendung konnte aufgezeigt und weitestgehend monetär bewertet werden, welche Vor- und Nachteile der Einsatz eines autonomen Shuttlebusses in diesem exemplarischen Vergleich und im aktuellen Entwicklungsstadium mit sich bringen. Durch die in dieser Dissertation durchgeführte Befragung der Nutzerperspektive konnte ergänzend bestätigt werden, dass unter anderem die Informiertheit über ein Mobilitätskonzeptes als auch dessen Reputation die Nutzungsabsicht potenzieller Nachfrager signifikant beeinflussen. Unter Berücksichtigung identifizierter Einschränkungen, kann das Kriteriensystem zum einen als valider Bewertungsrahmen für weitere Mobilitätskonzepte im frühen Entwicklungsstadium herangezogen werden. Außerdem bietet es eine systematisierte Grundlage, um in Verbindung mit weiteren Kriterien für die Bewertung der Angebotsqualität im Gesamtnetzzusammenhang auch im nachfolgenden seriellen Betrieb Verwendung finden zu können. Alles im Allem zeigt die Dissertation auf, dass einerseits die Wirtschaftlichkeit, die Umweltverträglichkeit sowie der Beitrag zur Angebotsqualität maßgeblichen Einfluss auf die Nachhaltigkeit eines Mobilitätskonzeptes ausüben. Andererseits wird auf die Relevanz kommunikativer Maßnahmen gegenüber der Bevölkerung zur Förderung des Erfolgspotenzials aufmerksam gemacht.:Inhalt 1 Einleitung ............................................................................................................... 1 1.1 Zielsetzung der Arbeit ....................................................................................... 2 1.2 Forschungsfragen und forschungsleitende Hypothesen ................................... 3 1.3 Wissenschaftlicher Erkenntnisprozess und empirisches Vorgehen ................... 7 1.4 Stand der Wissenschaft und Forschung ............................................................ 8 2 Fachwissenschaftliche Grundlagen ................................................................... 10 2.1 Urbanisierung .................................................................................................. 10 2.1.1 Definition und Abgrenzung des suburbanen Raumes ............................... 12 2.2 Mobilitätskonzepte ........................................................................................... 20 2.2.1 Definition und Abgrenzung des Begriffs Mobilitätskonzept ....................... 21 2.2.2 Die drei Wirkungsebenen eines Mobilitätskonzepts .................................. 23 2.3 Autonome Shuttlebusse .................................................................................. 26 2.3.1 Die Technologie des autonomen Fahrens ................................................ 27 2.3.3 Rechtliche Rahmenbedingungen .............................................................. 28 2.3.4 Vorstellung des Shuttlebusses .................................................................. 31 2.3.5 Faktoren der Akzeptanz und des Technologievertrauens in autonome Fahrfunktionen ................................................................................................... 35 2.4 Bewertungsverfahren öffentlicher Verkehrsprojekte ........................................ 44 2.4.1 Nutzen-Kosten-Analyse ............................................................................ 49 2.4.2 Nutzwertanalyse ........................................................................................ 51 2.4.3 Kosten-Wirksamkeits-Analyse................................................................... 53 2.4.4 Externe Effekte und öffentliche Güter ....................................................... 54 2.4.5 Externe Kosten des Verkehrs.................................................................... 57 2.4.6 Bewertungsansätze von externen Effekten ............................................... 62 2.5 Der ÖPNV in Deutschland ............................................................................... 66 2.5.1 Grundlegende Herausforderungen des ÖPNV .......................................... 67 2.5.2 Aktuelle Entwicklungen im ÖPNV ............................................................. 70 2.6 Kriterien in der Bewertung des ÖPNV-Angebots ............................................. 72 3 Identifikation und Aufstellung der Bewertungskriterien .................................. 80 3.1 Abgrenzung des Anwendungsbereichs ........................................................... 81 3.1.1 Ausschlusskriterien und Voraussetzungen ............................................... 82 3.2 Bewertung der ausgewählten Kriterien ............................................................ 87 3.3 Nutzereinschätzung gegenüber dem autonomen Shuttlebus im öffentlichen Personennahverkehr ............................................................................................. 94 3.3.1 Sicherstellung der Operationalisierung ..................................................... 95 3.3.2 Beschreibung der Stichproben .................................................................. 97 3.3.3 Auswertung der Befragungs-Items .......................................................... 104 3.3.4 Beantwortung der Hypothesen zur Nutzererwartung .............................. 122 4 Definition und Operationalisierung identifizierter Kriterien ........................... 131 4.1 Planungsziel 1: Erhöhung der Angebotsqualität des ÖPNV-Angebots .......... 131 4.1.1 Oberkriterium: Erhöhung der Bedienungsqualität des ÖPNV-Angebots . 131 4.1.2 Oberkriterium: Erhöhung der Beförderungsqualität ................................. 137 4.2 Planungsziel 2: Erhöhung der Wirtschaftlichkeit des ÖPNV-Angebots ......... 145 4.2.1 Oberkriterium: Investitionskosten ............................................................ 145 4.2.2 Oberkriterium: Betriebskosten ................................................................. 149 4.3 Planungsziel 3: Verbesserung der Umweltwirkungen des ÖPNV-Angebots . 153 4.3.1 Oberkriterium: Umweltverträglichkeit ...................................................... 154 4.4 Konsolidierung Kriteriensystem ..................................................................... 163 4.4.1 Veranschaulichung anhand des Pilotbetriebes Bad Birnbach ................. 164 4.4.2 Beantwortung der Forschungsfrage zur Anbieterseite ............................ 168 4.4.3 Fehlende Informationsgrundlagen und Unsicherheitsfaktoren ................ 170 5 Fazit und kritische Würdigung ......................................................................... 172 Literaturverzeichnis.............................................................................................. 175 Anhang .................................................................................................................. 185 Tabellenverzeichnis.............................................................................................. 189 Abbildungsverzeichnis ........................................................................................ 19

Bulmaca temelli öğrenme yaklaşımının ortaokul öğrencilerinin İngilizce dersine yönelik tutumlarına ve öz-yeterlik inançlarına etkisi

The overall aim of this research was to examine the effectiveness of puzzle-based learning approach on secondary school students’ attitudes and their self-efficacy beliefs in English lesson. The research employed the mixed model and quasi-experimental design with pre-test/post-test was applied. The working group was consisted of the 8th grade students who were selected from two classes and who learned at Elbistan Secondary School during the 2017-2018 academic year. The study was conducted with two groups; experimental group and control group. While lessons were taught based on puzzle-based learning approach in experimental group, in control group the lessons were taught according to the suggested methods of English lesson curriculum. At the end of the study, experimental group students’ attitudes and self-efficacy beliefs in English lesson scores increased within groups and between groups. The activities which were carried out in the context of puzzle-based learning were considered as effective applications by students. Observations done during the implementation process of puzzle-based learning in experimental group revealed that the students had fun and learned, and their active participation increased during lessonsBu araştırmanın genel amacı, bulmaca temelli öğrenme yaklaşımının ortaokul sekizinci sınıf öğrencilerinin İngilizce dersine yönelik tutum ve İngilizce öz-yeterlik inançlarına etkisini belirlemektir. Çalışmada hem nicel hem de nitel verilerin birlikte yer aldığı karma model kullanılmış ve deneysel desen olarak öntest-sontest kontrol gruplu yarı deneysel desen tercih edilmiştir. Çalışma grubu, 2017- 2018 eğitim-öğretim yılında Kahramanmaraş ili Elbistan ilçesindeki bir ortaokulun iki şubesindeki sekizinci sınıf öğrencilerinden oluşmaktadır. Araştırma, biri deney grubu diğeri kontrol grubu olmak üzere iki grupla uygulanmıştır. Deney grubunda dersler bulmaca temelli öğrenme yaklaşımına göre işlenirken, kontrol grubunda dersler İngilizce dersi öğretim programın öngördüğü yöntemlere dayalı olarak işlenmiştir. Çalışmanın sonucunda, bulmaca temelli öğrenme yaklaşımının uygulandığı deney grubu öğrencilerinin grup içinde ve gruplar arasında İngilizce dersine yönelik tutumlarının ve İngilizce öz-yeterlik inançlarının olumlu yönde arttığı ortaya çıkmıştır. Bulmaca temelli öğrenme bağlamında gerçekleştirilen etkinlikler, öğrenciler tarafından etkili uygulamalar olarak değerlendirilmiştir. Deney grubunda uygulama sürecinde yapılan gözlemler sonucunda bulmaca temelli öğrenme etkinlikleri aracılığıyla öğrencilerin eğlenip öğrendikleri ve derslerde aktif katılımlarının arttığı görülmüştü