239 research outputs found
Humanistic Criminology: Is It Possible?
A humanistic criminology is one that would be oriented to human betterment and fulfillment, as opposed to conventional criminology oriented to the control of crime and suppression of offenders. Some of the obstacles that stand in the way of developing a humanistic criminology, as well as some of the reasons why these obstacles do not necessarily preclude its being established, are addressed. Some reasons why humanistic criminology is desirable are suggested. Given that humanistic criminology is viable a critique of contemporary schools of criminology/criminal justice is offered and a number of suggestions are made regarding what an academic department of criminology oriented to humanism would study and emphasize in its curriculum and goals
Semantische Klassifikation von urbanen Verkehrszenarien für die Absicherung des automatischen Fahrens
The safety argumentation of an automated vehicle is an essential condition before its use on public roads. For this reason, a thorough Verification and Validation (V&V) process is a fundamental aspect of the development and commercial release for every automated vehicle. In recent years, a number of scientific publications have reasoned that a distance- based V&V approach, aimed at providing a stochastic safety argument by achieving a desired failure-rate over a defined testing distance, will not be feasible to implement for automated vehicles. The main reason for this is the fact that the distance required to be driven with development vehicles exceeds economical and practical limits by far. To overcome this challenge, scenario-based V&V approaches are currently a subject of many research activities. These methodologies aim to evaluate the safety of an automated vehicle by testing it in a variety of different traffic scenarios. This allows to decompose the safety V&V into smaller units in the form of scenarios instead of having to achieve one large statistical argument for the safety of the system. However, urban traffic scenarios themselves form a complex, high dimensional state-space, which makes it challenging to argue for the completeness of scenario-based V&V approaches. This work aims to address this challenge through a semantic classification of urban traffic scenarios. By extracting them in a structured manner from large volumes of recorded driving data, it is possible to analyze them statistically and to make empirical, data-driven contributions to the V&V process of automated vehicles. To this end, a catalog of driving maneuvers is introduced to describe the behavior of vehicles in urban traffic on a semantic level. Next, algorithms for the automated classification of these maneuvers are implemented and evaluated with respect to their detection accuracy. Based on this automated maneuver classification, an empirical analysis of urban traffic scenario diversity is conducted. Here, a special focus is put on saturation effects during data collection as well as the observed exposure of various semantic scenario elements. The results of the investigations provide some of the first quantitative insights into the Long Tail-problem of automated driving V&V, which is often mentioned in current literature in this field. From the empirical findings it is further concluded that a semantic scenario classification has the potential to contribute substantially to a data-driven, scenario-based safety argumentation for automated vehicles.Der Sicherheitsnachweis eines automatischen Fahrzeugs ist ein zwingend notwendiger Schritt, den es vor dessen Markteinführung auf öffentlichen Straßen zu absolvieren gilt. Aus diesem Grund ist ein schlüssiger Prozess zur Verifikation und Validierung (kurz V&V) elementarer Bestandteil der Entwicklungsarbeit jedes automatischen Fahrsystems. In den letzten Jahren kamen verschiedene wissenschaftliche Veröffentlichungen zu dem Schluss, dass ein distanzbasierter V&V-Ansatz, bei dem ein Sicherheitsnachweis statistisch durch das Erreichen einer angestrebten Fehlerrate über eine zuvor festgelegte Referenzdistanz erbracht wird, für automatische Fahrzeuge aller Wahrscheinlichkeit nach nicht anwendbar sein wird. Dies ist vor allem darin begründet, dass die notwendigen Testdistanzen ein ökonomisch vertretbares Maß bei Weitem übersteigen würden. Aus diesem Grund sind szenarienbasierte V&V-Ansätze derzeit Gegenstand vieler Forschungsaktivitäten, in denen die Sicherheit des automatisierten Fahrzeugs in einer Vielzahl von Verkehrsszenarien nachgewiesen werden soll. Diese Arbeit befasst sich mit der semantischen Klassifikation von urbanen Verkehrs- szenarien, um diese in großen Datenmengen strukturiert erfassen und statistisch für den V&V-Prozess automatisierter Fahrzeuge analysieren zu können. Zu diesem Zweck wird zunächst ein Fahrmanöverkatalog zur semantischen Beschreibung urbanen Fahrverhaltens entwickelt. Anschließend werden Algorithmen zur automatischen Klassifikation dieser Fahrmanöver in aufgenommenen Fahrzeugmessdaten implementiert und hinsichtlich ihrer Erkennungsgüte evaluiert. Basierend auf dieser automatischen Klassifikation wird eine empirische Analyse urbaner Verkehrsszenarien durchgeführt, mit einem besonderen Augenmerk auf Sättigungseffekten bei der Datensammlung sowie der Exposition einzelner semantischer Szenarienelemente. Die Untersuchungen liefern erste quantitative Nachweise des vielfach in der wissenschaftlichen Literatur diskutierten Long-Tail-Problems bei der Absicherung automatischer Fahrfunktionen. Aus den empirischen Erkenntnissen wird geschlussfolgert, dass eine semantische Szenarienklassifikation das Potenzial hat, einen wichtigen Beitrag zur einer datengetriebenen, szenarienbasierten Sicherheitsargumentation für automatisierte Fahrzeuge zu leisten
Die lymphozytäre und humorale Immunrekonstitution nach allogener Stammzelltransplantation
Der Prozess der Immunrekonstitution nach allogener hämatopoetischer Stammzelltransplantation (HSCT) ist komplex und bis heute nicht vollständig verstanden; gleichwohl sind der Genesungsprozess und das Überleben von Patienten nach Stammzelltransplantation in hohem Maße abhängig von der Wiedererlangung einer vollumfänglichen immunologischen Funktion. Diese Dissertationsschrift untersucht vor diesem Hintergrund die Immunrekonstitution des zellulären und humoralen Systems bei 136 erwachsenen Stammzellempfängern 3 bis 21 Monate nach allogener HSCT unter Berücksichtigung verschiedener Einfluss nehmender Faktoren.
Bis Ende des Untersuchungszeitraumes erreichte die Rekonstitution des T-Zellsystems in 45%, die des B-Zellkompartiments in 50% der Fälle ihren jeweiligen Normwertbereich; die Rekonstitution der CD8+ T-Lymphozyten war dabei deutlich erfolgreicher als die CD4+ T-Lymphozyten. Die NK-Zelllinie erreichte nach 21 Monaten zu 100% normale Werte. Im Gegensatz zu der in Teilen defizitären zellulären Erholung wies ein Großteil der Patienten 21 Monate nach allogener HSCT normwertige Serum-Immunglobuline auf.
Nach der Analyse verschiedener Parameter auf die Immunrekonstitution ließ sich eine frühe CMV-Infektion als stärkste Einflussvariable auf die Immunrekonstitution nach allogener HSCT identifizieren. Insbesondere die Wachstumsrate CD8+ T-Lymphozyten sowie der Immunglobuline wurde durch die Infektion langfristig erhöht, wobei die Spezifität mit den eingesetzten Methoden nicht geklärt werden konnte. Bei einer Prävalenz von 40% kam der chronischen Graft-versus-Host Disease im Kontext der zellulären und humoralen Rekonvaleszenz erstaunlicherweise eine untergeordnete Rolle zu; herauszustellen verbleibt an dieser Stelle jedoch die gestörte B-Zellrekonstitution bei stattgehabter chronischer Graft- versus-Host Disease. Während sich der Einsatz dosisreduzierter Regime in Bezug auf die Immunrekonstitution im Rahmen dieser Arbeit als weitestgehend gleichrangig gegenüber klassisch myeloablativen Konditionierungsregimen erwies und Alterseffekte ebenfalls nur schwach ausgeprägt waren, soll an dieser Stelle die erfolgreiche Immunrekonstitution bei älteren Patienten als Resultat moderner intensitätsreduzierter Konditionierungen betont werden. Ferner, und bisher in dieser Form nicht beschrieben, konnte der Einsatz von Alemtuzumab gegenüber Antithymozytenglobulin als nachhaltiger Einflussfaktor auf die Rekonstitution CD8+ T-Lymphozyten ermittelt werden.
Die Ausbildung einer Monoklonalen Gammopathie unklarer Signifikanz (MGUS) hatte keinen Einfluss auf die lymphozytäre und humorale Rekonstitution nach allogener HSCT. Auch konnte trotz einer relativen Häufung bei Myelompatienten kein Zusammenhang zwischen dem Auftreten einer MGUS und der zur Transplantation führenden Grunderkrankung gefunden werden. Insgesamt zeigten Patienten mit MGUS jedoch ein signifikant erhöhtes Vorkommen an chronischer Graft versus Host Disease. Eine CMV-Reaktivierung als Auslöser einer MGUS konnte ausgeschlossen werden
Do female offenders differ? Comparing the criminal histories of serious violent perpetrators with a control sample
In view of earlier research, female offenders have not received as much attention as male perpetrators. Thus, the research aimed to gain insight into the types of offences committed by serious violent female offenders (n = 206; those who had committed grievous bodily harm, attempted murder, or homicide) and to explore differences with control female perpetrators (n = 447); control offenders were matched according to age and year of offence of the serious violent offenders. The purpose was to, therefore, gather an understanding of female offenders and to determine if the serious violent perpetrators differed from the control sample. A UK police force provided data of offences committed between April 2001 and April 2011. Descriptive information was analysed, with comparisons being made using Mann–Whitney U tests and chi-square analyses. About 72.3% (n = 149) of serious violent offenders had one or more recorded convictions and were significantly more likely to have committed a previous violent offence than the control sample. On the other hand, control perpetrators had a higher likelihood of having previously committed a theft-related offence, when compared to serious violent females. Therefore, the findings indicate the types of offences committed by female offenders and highlight the differences between serious violent perpetrators and offenders in the control sample. The implications and limitations are discussed
Assessment of the range of the HIV-1 infectivity enhancing effect of individual human semen specimen and the range of inhibition by EGCG
Recently, it has been shown that human ejaculate enhances human immunodeficiency virus 1 (HIV-1) infectivity. Enhancement of infectivity is conceived to be mediated by amyloid filaments from peptides that are proteolytically released from prostatic acid phosphatase (PAP), termed Semen-derived Enhancer of Virus Infection (SEVI). The aim of this study was to test the range of HIV-1 infectivity enhancing properties of a large number of individual semen samples (n = 47) in a TZM-bl reporter cell HIV infection system. We find that semen overall increased infectivity to 156% of the control experiment without semen, albeit with great inter- and intraindividual variability (range -53%-363%). Using transmission electron microscopy, we provide evidence for SEVI fibrils in fresh human semen for the first time. Moreover, we confirm that the infectivity enhancing property can be inhibited by the major green tea ingredient epigallocatechin-3-gallate (EGCG) at non-toxic concentrations. The median inhibition of infection by treatment with 0.4 mM EGCG was 70.6% (p < 0.0001) in our cohort. Yet, there were substantial variations of inhibition and in a minority of samples, infectivity enhancement was not inhibited by EGCG treatment at all. Thus, topical application of EGCG may be a feasible additional measure to prevent the sexual transmission of HIV. However, the reasons for the variability in the efficacy of the abrogation of semen-mediated enhancement of HIV-1 infectivity and EGCG efficacy have to be elucidated before therapeutic trials can be conducted
Alterations in function and distribution of regulatory T Cells (Tregs) may blunt vaccine induced immune responses in HIV infection
Downregulation of the 5’-ectonucleotidase CD73 of CD8+ CTL of HIV infected patients correlates with immune activation and diminished IL-2 production
Palate Lung Nasal Clone (PLUNC), a Novel Protein of the Tear Film: Three-Dimensional Structure, Immune Activation, and Involvement in Dry Eye Disease (DED)
Citation: Schicht M, Rausch F, Beron M, et al. Palate lung nasal clone (PLUNC), a novel protein of the tear film: three-dimensional structure, immune activation, and involvement in dry eye disease (DED). Invest Ophthalmol Vis Sci. 2015;56:7312-7323. DOI:10.1167/iovs.15-17560 PURPOSE. Palate Lung Nasal Clone (PLUNC) is a hydrophobic protein belonging to the family of surfactant proteins that is involved in fluid balance regulation of the lung. Moreover, it is known to directly act against gram-negative bacteria. The purpose of this study was to investigate the possible expression and antimicrobial role of PLUNC at the healthy ocular surface and in tears of patients suffering from dry eye disease (DED). METHODS. Bioinformatics and biochemical and immunologic methods were combined to elucidate the structure and function of PLUNC at the ocular surface. Tissue-specific localization was performed by using immunohistochemistry. The PLUNC levels in tear samples from non-Sjögren's DED patients with moderate dry eye suffering either from hyperevaporation or tear deficiency were analyzed by ELISA and compared with tears from healthy volunteers. RESULTS. Palate Lung Nasal Clone is expressed under healthy conditions at the ocular surface and secreted into the tear film. Protein modeling studies and molecular dynamics simulations performed indicated surface activity of PLUNC. In vitro experiments revealed that proinflammatory cytokines and bacterial supernatants have only a slight effect on the expression of PLUNC in HCE and HCjE cell lines. In tears from DED patients, the PLUNC concentration is significantly increased (7-fold in evaporative dry eye tears and 17-fold in tears from patients with tear deficiency) compared with healthy subjects. CONCLUSIONS. The results show that PLUNC is a protein of the tear film and suggest that it plays a role in fluid balance and surface tension regulation at the ocular surface
A short-term plastic adherence incubation of the stromal vascular fraction leads to a predictable GMP-compliant cell-product
Introduction: Mesenchymal stromal/stem cells (MSCs) derived from fat tissue are an encouraging tool for regenerative medicine. They share properties similar to the bone marrow-derived MSCs, but the amount of MSCs per gram of fat tissue is 500x higher. The fat tissue can easily be digested by collagenase, releasing a heterogeneous cell fraction called stromal vascular fraction (SVF) which contains a variable amount of stromal/stem cells. In Europe, cell products like the SVF derived from fat tissue are considered advanced therapy medicinal product (ATMPs). As a consequence, the manufacturing process has to be approved via GMP-compliant process validation. The problem of the process validation for SVF is the heterogeneity of this fraction. Methods: Here, we modified existing purification strategies by adding an additional plastic adherence incubation of maximal 20 hours after SVF isolation. The resulting cell fraction was characterized and compared to SVF as well as cultivated adipose-derived stromal/stem cells (ASCs) with respect to viability and cell yield, the expression of surface markers, differentiation potential and cytokine expression. Results: Short-term incubation significantly reduced the heterogeneity of the resulting cell fraction compared to SVF. The cells were able to differentiate into adipocytes, chondrocytes, and osteoblasts. More importantly, they expressed trophic proteins which have been previously associated with the beneficial effects of MSCs. Furthermore, GMP compliance of the production process described herein was acknowledged by the national regulatory agencies (DE_BB_01_GMP_2017_1018). Conclusion: Addition of a short purification-step after the SVF isolation is a cheap and fast strategy to isolate a homogeneous uncultivated GMP-compliant cell fraction of ASCs
Improved in vitro test procedure for full assessment of the cytocompatibility of degradable magnesium based on ISO 10993-5/-12
Magnesium (Mg)-based biomaterials are promising candidates for bone and tissue regeneration. Alloying and surface modifications provide effective strategies for optimizing and tailoring their degradation kinetics. Nevertheless, biocompatibility analyses of Mg-based materials are challenging due to its special degradation mechanism with continuous hydrogen release. In this context, the hydrogen release and the related (micro-) milieu conditions pretend to strictly follow in vitro standards based on ISO 10993-5/-12. Thus, special adaptions for the testing of Mg materials are necessary, which have been described in a previous study from our group. Based on these adaptions, further developments of a test procedure allowing rapid and effective in vitro cytocompatibility analyses of Mg-based materials based on ISO 10993-5/-12 are necessary. The following study introduces a new two-step test scheme for rapid and effective testing of Mg. Specimens with different surface characteristics were produced by means of plasma electrolytic oxidation (PEO) using silicate-based and phosphate-based electrolytes. The test samples were evaluated for corrosion behavior, cytocompatibility and their mechanical and osteogenic properties. Thereby, two PEO ceramics could be identified for further in vivo evaluations
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