Why be yourself? Kantian Respect and Frankfurtian Identification

Harry Frankfurt has claimed that some of our desires are ‘internal', i.e., our own in a special sense. I defend the idea that a desire's being internal matters in a normative, reasons‐involving sense, and offer an explanation for this fact. The explanation is Kantian in spirit. We have reason to respect the desires of persons in so far as respecting them is a way to respect the persons who have them (in some cases, ourselves). But if desires matter normatively in so far as they belong to persons, then it matters whether they really do belong to the persons who have them. Thus Kantian considerations explain why identification (or internality) is a normatively relevant category. This account is superior to others, and does not lead to reasons bootstrapping or a self‐centred conception of deliberatio

The effect of chronic constriction injury to the sciatic nerve on myofibrillar protein synthesis in rat tibialis anterior

This doctorate comprised several projects investigating skeletal muscle metabolism in neuromuscular diseases, resulting in multiple publications. Based on the doctoral degree regulations of the Charité Berlin, this dissertation will focus exclusively on the first project that led to a “top journal” publication. In this project I investigated skeletal muscle protein turnover in rat tibialis anterior (TA) following chronic constriction injury to the sciatic nerve. While changes to muscle protein metabolism after nerve transection are relatively well understood, knowledge on other peripheral nerve injuries is sparse. Chronic constriction injury was caused by implanting a cuff tightly around the sciatic nerve of male Sprague-Dawley rats between 21 to 22 weeks of age (n=10). Four weeks after surgically inducing the injury, bodyweight of the animals did not change significantly while body composition was altered. Lean body mass decreased by 3.7 % from 75.4 % (± 2.3 %) to 71.7 % (± 1.3 %) which was accompanied by a concomitant increase in bodyfat by 2.7 % from 18.3 % (± 2.1 %) to 21.2 % (± 2.5 %) (p<0.01, p<0.05). Locally, the constriction injury had caused a decrease in muscle mass of 66 % (±10 %) and 50 % (± 17 %) of the TA and extensor digitorum longus, respectively (p<0.001, p<0.001). We found that this loss of mass was predominantly caused by a decrease in fiber diameter rather than fiber number: Average fiber diameter of type I fibers in the TA decreased by 38 % (47 µm ±3 µm [control] to 34 µm ± 3 µm [damaged]), type II a fibers by 30 % (47 µm ± 4 µm [control] to 36 µm ± 7 µm [damaged]) and type II b fibers by 70 % (56 µm ± 6 µm [control] to 33 µm ± 6 µm [damaged]) (p<0.01, p<0.05, p<0.001) while fiber number did not decrease in a statistically significant manner. We used stable isotope labeling via deuterium oxide to investigate changes of myofibrillar protein synthesis during the last two weeks of the intervention. Despite substantial loss of muscle mass and apparent fiber atrophy, myofibrillar protein synthesis was increased in every single animal by an average 55 % in nerve damaged TA compared to the contralateral control leg (3.23 ± 0.72 [damaged] to 2.09 ± 0.26%∗day−1 [control]) (p<0.001). This increase in myofibrillar protein synthesis was supported by a coinstantaneous increase in the protein levels of p70S6K1 by 33 % from 1.8 ± 0.2 to 2.4 ± 0.3 AU (p<0.01). In conclusion, we found that constriction injury of the sciatic nerve is accompanied by a substantial decrease in muscle mass and muscle fiber diameter despite a significant increase in myofibrillar protein synthesis and anabolic signaling protein levels. As such, to ameliorate muscle loss in chronic nerve constriction injury, targeting myofibrillar protein breakdown could hold more promise than targeting the already increased synthesis of myofibrillar proteins.Diese Promotion befasste sich mit Projekten zum Stoffwechsel der Skelettmuskulatur in neuromuskulären Erkrankungen, wovon mehrere in Publikationen resultierten. Basierend auf der Promotionsordnung der Charité Berlin behandelt diese Dissertation ausschließlich das erste Projekt, aus welchem eine „Top Publikation“ hervorging. Dieses Projekt untersuchte Änderungen des Proteinstoffwechsels in Muskelgruppen, die von chronischer Nervenkonstriktion betroffen sind. Während ähnliche Untersuchungen zu vollständig denervierten Muskeln publiziert sind, ist wenig über den Muskelstoffwechsel in anderen peripheren Nervenverletzungen bekannt. Eine chronische Nervenkonstriktion des N. ischiadicus wurde durch die Implantation einer Manschette um den Nerv 21-22 Wochen alter Sprague-Dawley Ratten (n=10) hervorgerufen. Vier Wochen postoperativ war das Körpergewicht der Tiere unverändert, anders als die Körperkomposition: Die fettfreie Masse reduzierte sich um 3.7 % von 75.4 % (± 2.3 %) auf 71.7 % (± 1.3 %), was von einem gleichzeitigen Anstieg des Fettanteils um 2.7 % von 18.3 % (± 2.1 %) auf 21.2 % (± 2.5 %) begleitet wurde (p<0.01, p<0.05). Lokal verursachte der Nervenschaden eine Reduktion des Muskelgewichtes des M. tibialis anterior (TA) und M. extensor digitorum longus um 66 % (± 10 %) und 50 % (± 17 %) (p<0.001, p<0.001). Diese Reduktion der Muskelmasse ließ sich primär auf Faseratrophie zurückführen: Der Durchmesser der Typ I Fasern reduzierte sich im TA um 38 % (47 μm ± 3 μm [Kontrolle] zu 34 μm ± 3 μm [Intervention]), der Typ II A Fasern um 30 % (47 μm ± 4 μm [Kontrolle] zu 36 μm ± 7 μm [Intervention]) und der Typ II B Fasern um 70 % (56 μm ± 6μm [Kontrolle] zu 33 μm ± 6 μm [Intervention]) (p<0.01, p<0.05, p<0.001), während sich die Faserzahl nicht signifikant unterschied. Um die Syntheserate von myofibrillärem Protein zu untersuchen, verwendeten wir während der letzten zwei Wochen der Intervention Isotopenmarkierung durch Deuteriumoxid. Trotz des starken Verlustes an Muskelmasse sahen wir einen signifikanten Anstieg der myofibrillären Proteinsynthese von durchschnittlich 55 % im TA des nervengeschädigten Beines (3.23 ± 0.72 [Intervention] zu 2.09 ± 0.26 %∗Tag−1 [Kontrolle]) (p<0.001). Jedes Tier zeigte einen Anstieg der Proteinsyntheserate mit der Intervention. Dieser Anstieg der Syntheserate wurde von einer simultanen Zunahme des Signalproteins p70S6K1 um 33 % (1.8 ± 0.2 AU [Kontrolle] zu 2.4 ± 0.3 AU [Intervention] begleitet (p<0.01), welches dafür bekannt ist, die Proteinsynthese und Zellproliferation zu aktivieren. Zusammenfassend demonstriert diese Arbeit, dass chronische Konstriktion des N. ischiadicus zu starkem Muskelschwund und Faseratrophie führt, welche von einem Anstieg der Muskelproteinsynthese und anaboler Signalproteine begleitet wird. Strategien, welche die Proteolyserate von myofibrillärem Protein verlangsamen, könnten daher vielversprechendere Interventionsziele bei Nervenkonstriktion darstellen als jene, die das Verstärken der bereits erhöhten Muskelproteinsyntheserate zum Ziel haben

Nerve damage induced skeletal muscle atrophy is associated with increased accumulation of intramuscular glucose and polyol pathway intermediates

Perturbations in skeletal muscle metabolism have been reported for a variety of neuromuscular diseases. However, the role of metabolism after constriction injury to a nerve and the associated muscle atrophy is unclear. We have analyzed rat tibialis anterior (TA) four weeks after unilateral constriction injury to the sciatic nerve (DMG) and in the contralateral control leg (CTRL) (n = 7) to investigate changes of the metabolome, immunohistochemistry and protein levels. Untargeted metabolomics identified 79 polar metabolites, 27 of which were significantly altered in DMG compared to CTRL. Glucose concentrations were increased 2.6-fold in DMG, while glucose 6-phosphate (G6-P) was unchanged. Intermediates of the polyol pathway were increased in DMG, particularly fructose (1.7-fold). GLUT4 localization was scattered as opposed to clearly at the sarcolemma. Despite the altered localization, we found GLUT4 protein levels to be increased 7.8-fold while GLUT1 was decreased 1.7-fold in nerve damaged TA. PFK1 and GS levels were both decreased 2.1-fold, indicating an inability of glycolysis and glycogen synthesis to process glucose at sufficient rates. In conclusion, chronic nerve constriction causes increased GLUT4 levels in conjunction with decreased glycolytic activity and glycogen storage in skeletal muscle, resulting in accumulation of intramuscular glucose and polyol pathway intermediates

Statutory Retirement Age and Lifelong Learning

The employability of an aging population in a world of continuous technical change is top of the political agenda. Due to endogenous human capital depreciation, the effective retirement age is often below statutory retirement age resulting in unemployment among older workers. We analyze this phenomenon in a putty-putty human capital vintage model and focus on education and the speed of human capital depreciation. Introducing a two-stage education system with initial schooling and lifelong learning, not even lifelong learning turns out to be capable of aligning economic and statutory retirement. However, lifelong learning can increase the number of people reaching statutory retirement age and hence reduce the problem of old age unemployment in an aging society.lifelong learning, retirement, unemployment, education system

Age- and wavelength-dependency of drosophila larval phototaxis and behavioral responses to natural lighting conditions

Animals use various environmental cues as key determinant for their behavioral decisions. Visual systems are hereby responsible to translate light-dependent stimuli into neuronal encoded information. Even though the larval eyes of the fruit fly Drosophila melanogaster are comparably simple, they comprise two types of photoreceptor neurons (PRs), defined by different Rhodopsin genes expressed. Recent findings support that for light avoidance Rhodopsin5 (Rh5) expressing photoreceptors are crucial, while Rhodopsin6 (Rh6) expressing photoreceptors are dispensable under laboratory conditions. However, it remains debated how animals change light preference during larval live. We show that larval negative phototaxis is age-independent as it persists in larvae from foraging to wandering developmental stages. Moreover, if spectrally different Rhodopsins are employed for the detection of different wavelength of light remains unexplored. We found that negative phototaxis can be elicit by light with wavelengths ranging from ultraviolet (UV) to green. This behavior is uniquely mediated by Rh5 expressing photoreceptors, and therefore suggest that this photoreceptor-type is able to perceive UV up to green light. In contrast to laboratory our field experiments revealed that Drosophila larvae uses both types of photoreceptors under natural lighting conditions. All our results, demonstrate that Drosophila larval eyes mediate avoidance of light stimuli with a wide, ecological relevant range of quantity (intensities) and quality (wavelengths). Thus, the two photoreceptor-types appear more likely to play a role in different aspects of phototaxis under natural lighting conditions, rather than color discrimination

The forgotten channels: charged Higgs boson decays to a W±W^\pm and a non-SM-like Higgs boson

The presence of charged Higgs bosons is a generic prediction of multiplet extensions of the Standard Model (SM) Higgs sector. Focusing on the Two-Higgs-Doublet-Model (2HDM), we discuss the charged Higgs boson collider phenomenology in the theoretically and experimentally viable parameter space. While almost all existing experimental searches at the LHC target the fermionic decays of charged Higgs bosons, we point out that the bosonic decay channels -- especially the decay into a non-SM-like Higgs boson and a $W$ boson -- often dominate over the fermionic channels. Moreover, we revisit two genuine BSM effects on the properties of the discovered Higgs boson -- the charged Higgs contribution to the diphoton rate and the Higgs decay to two light Higgs bosons -- and their implication for the charged Higgs boson phenomenology. As main result of the present paper, we propose five two-dimensional benchmark scenarios with distinct phenomenological features in order to facilitate the design of dedicated LHC searches for charged Higgs bosons decaying into a $W$ boson and a light, non-SM-like Higgs boson.Comment: 57 pages, 26 figures, data tables for cross sections and benchmark scenarios included as ancillary files, updated text to match journal versio

In Vivo Corrosion of Two Novel Magnesium Alloys ZEK100 and AX30 and Their Mechanical Suitability as Biodegradable Implants

In magnesium alloys, the components used modify the alloy properties. For magnesium implants in contact with bone, rare earths alloys are commonly examined. These were shown to have a higher corrosion resistance than other alloys and a high mechanical strength, but their exact composition is hard to predict. Therefore a reduction of their content could be favorable. The alloys ZEK100 and AX30 have a reduced content or contain no rare earths at all. The aim of the study was to investigate their in vivo degradation and to assess the suitability of the in vivo μCT for the examination of their corrosion. Implants were inserted in rabbit tibiae. Clinical examinations, X-rays and in vivo μCT scans were done regularly. Afterwards implants were analyzed with REM, electron dispersive X-ray (EDX), weighing and mechanical testing. The in vivo μCT is of great advantage, because it allows a quantification of the corrosion rate and qualitative 3D assessment of the corrosion morphology. The location of the implant has a remarkable effect on the corrosion rate. Due to its mechanical characteristics and its corrosion behavior, ZEK100 was judged to be suitable, while AX30, which displays favorable degradation behavior, has too little mechanical strength for applications in weight bearing bones

Assessing the Impact of Tutorial Services

This is a preliminary report assessing the impact of tutorial services on student performance. We discuss a statistical approach, and why regression models do not appear suitable for the analysis

Grundbildung im Strafvollzug: Bedarfe, Bedingungen und Ziele

Mit dieser aktuellen Bestandsaufnahme der Alphabetisierungs- und Grundbildungskurse im deutschen Strafvollzug schließen die Autoren eine Lücke in der Datenerhebung und -analyse. Bedarfe und Bedingungen wurden in qualitativen Interviews mit Experten, Lehrenden und Häftlingen festgestellt und in den rechtlichen Rahmen eingeordnet. Die Autoren betrachten qualitative und quantitative Indikatoren zur Alphabetisierungsarbeit mit Straffälligen und liefern damit eine Basis für weitere Forschungsarbeiten zum Thema. Ein Überblick über die Anzahl der Angebote vervollständigt das Bild. Die Studie ist ein Teilergebnis des BMBF-Projekts RAUS (Resozialisierung durch Alphabetisierung und Übergangsmanagement von Straffälligen). Ein wesentliches Projektziel ist die Etablierung der Grundbildung im Strafvollzug, damit sich für Ex-Häftlinge die Chancen auf dem Arbeitsmarkt verbessern und ein bürgerliches Leben möglich wird.This current stock-take of Literacy and Basic Education (Alphabetsierungs- und Grundbildung) courses in the German prison system closes a gap in data collection and analysis. Needs and requirements were ascertained in qualitative interviews with experts, teachers and inmates and were applied to the legal framework. The authors inspect qualitative and quantitative indicators for literacy work with inmates and deliver a foundation for further research on the topic. An overview of the number of offerings rounds off the view. The study is part of the findings of the BMBF project RAUS (Resocialisation by Way of Literacy Training and Transition Management for Offenders - Resozialisierung durch Alphabetisierung und Übergangsmanagement von Straffälligen). One important project objective is the establishment of basic education in the prison system to allow ex convicts better chances in the job market and a normal life in society

Temperature dependence of tropospheric ozone under NOx reductions over Germany

Due to the strong temperature dependence of surface ozone concentrations (O3), future warmer conditions may worsen ozone pollution levels despite continued efforts on emission controls of ozone precursors. Using longterm measurements of hourly O3 concentrations co-located with NOx concentrations in stations distributed throughout Germany, we assess changes in the climate penalty in summertime, defined as the slope of ozonetemperature relationship during the period 1999?2018. We find a stronger temperature sensitivity in the urban stations over the southwestern regions, especially in the first period of the study (1999?2008). We show a decrease in the climate penalty in most of stations during the second period of the study (2009?2018), with some exceptions (e.g. Berlin) where the climate penalty did not show significant changes. A key motivation of this study is to provide further insights into the impacts of NOx reductions in the O3-temperature relationship. For that, we propose a statisti-cal approach based on Generalized Additive Models (GAMs) to describe ozone production rates, inferred from hourly observations, as a function of NOx and temperature, among other variables relevant during the O3 production. The GAMs confirm lower O3 production rates during the second period (2009?2018) at most of the stations and a decreasing sensitivity to temperature. We observe that a large number of stations are transitioning to NOx-limited chemistry, consistent with a decreasing temperature dependence of O3 at moderate-high temperatures as a result of sustained NOx reductions. Moreover, the GAMs results showed changes in the shape of the function representing the O3-temperature relationship when comparing the first and second period, which suggest changes in VOC influencing the temperature dependence of O3. From these results, we infer effective VOC reductions over time that have also contributed to the observed decrease of O3 production rates. Thus, our analysis indicates that emissions reductions have been effective in a number of stations, particularly in the southwestern regions. However, we notice that in a few stations (e.g. Berlin) additional emission reductions should be required to effectively mitigate the temperature dependence of O3