601 research outputs found

    A Historical Examination of Punishment and Forgiveness in Literature for Children

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    The study of forgiveness gained momentum in the 1980\u27s when scientists were interested in finding a link between forgiveness and its benefits to mental health. The research resulted in a plethora of published books on the topic of forgiveness, found in the self-help section of many booksellers. However, the topic of forgiveness is often evident in literature for adults and for children, as well. This concept as seen in children\u27s literature has undergone changes over history. This final project analyzes select picture books and books for independent readers and adopts a historical perspective in order to illuminate a historical shift in how punishment and forgiveness play out in literature for children

    Probleme des Insolvenzplanverfahrens

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    The paper analyses options in case of insolvency. Although insolvency plans empirically are very successful, they are not used very much. Reasons that prevent their application and possibilities for their promotion are discussed. --Insolvenz,Insolvenzplan,Insolvenzverwalter,Planinitiativrecht,Gläubigerversammlung,Entscheidungssituation,Pre-Packaged-Plan,Eigenverwaltung,insolvency,bankruptcy code,liquidation,liquidator,insolvency plan,chapter 11 plan,Pre-Packaged-Plan

    Untersuchungen zur Reproduktion und Kälberentwicklung in ökologisch bewirtschafteten Mutterkuhherden

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    Untersucht wurden an 901 Mutterkühen der Einfluss der Länge des Zeitintervalls zwischen der Kalbung und der Zustellung des Zuchtbullen auf die Fruchtbarkeitsleistungen der Mutterkühe sowie die Fruchtbarkeit von Mutterkühen mit im Jahresverlauf unterschiedlichen Kalbe- und Belegungszeiträumen. Mit dem Einschränken des Intervalls zwischen der Kalbung und der Zustellung des Zuchtbullen unter 22 Tage wird die maximale Zahl Kalbungen pro Kuh und Jahr ermöglicht. Gleichzeitig verschiebt sich die Kalbeperiode im Jahresverlauf und die Kalbezeit wird verlängert. Die Verlängerung dieses Zeitintervalls bewirkt eine konzentriertere Kalbeperiode, aber auch weniger Kalbungen pro Kuh und Jahr. Für durchschnittlich eine Kalbung pro Kuh und Jahr und gleichzeitig eine gedrängte und im Jahresverlauf konstante Kalbeperiode ist die Zustellung des Deckbullen 40 bis 50 Tage nach der Kalbung zu empfehlen. In der Zeit unmittelbar vor Ende des Winters sowie während und kurz nach dem Weideaustrieb konzipieren durch die schlechte Körperkondition der Kühe nur wenige Tiere. Deshalb sollten, um eine Verlängerung der Kalbeperiode zu vermeiden, in diesem Zeitabschnitt Mutterkühe nicht belegt werden. Defizite der Trächtigkeitsrate können in kurzer Zeit kompensiert werden und sind deshalb für die Wahl der geeigneten Kalbeperiode von geringer Bedeutung. Die Daten von je 30 Kälbern mit und ohne Konzentratzufütterung erbrachten Erkenntnisse zur Kraftfutteraufnahme von Mutterkuhkälbern aus der Winterkalbung während der Stallhaltungsperiode und dessen Einfluss auf die Körpermasseentwicklung der Kälber. Vor dem 40. Lebenstag nehmen nur sehr wenige Mutterkuhkälber aus der Winterkalbung Kraftfutter auf. Ab 70 Tagen Lebensalter bringt die Zufütterung von Konzentraten bis zum Weideaustrieb Vorteile bei der Körpermasseentwicklung gegenüber Kälbern ohne Konzentratzufütterung. Nach der Einstellung der Konzentratfütterung mit Weideaustrieb haben zugefütterte Kälber erhebliche Umstellungsprobleme. Die Kälber ohne Konzentrataufnahme gleichen während der Weideperiode die Körpermassedefizite aus der Stallhaltung durch kompensatorisches Wachstum annähernd aus. Die Konzentratfütterung an Kälber aus der Winterkalbung während der Stallhaltungsperiode beeinflusst, wenn sie während der nachfolgenden Weidehaltung nicht fortgesetzt werden soll, das wirtschaftliche Ergebnis der Mutterkuhhaltung negativ. 40 Mutterkuhkälber aus der Sommerkalbung wurden nach Weideabtrieb im Stall mit Kraftfutter zugefüttert und tierindividuell der Einfluss der aufgenommenen Kraftfuttermenge auf die Körpermasseentwicklung der Kälber ermittelt. Der Beginn der Kraftfutteraufnahme, die täglichen Verzehrsmengen und die gesamt aufgenommene Menge sind zwischen älteren Mutterkuhkälbern auf Grund unterschiedlicher Milchmengen der Mutterkühe sowie individueller Vorlieben der Tiere stark differenziert. Da Kälber mit hoher Konzentrataufnahme weniger Grundfutter aufnehmen und Luxuskonsum betreiben, ist die Limitierung der Verzehrsmengen zu empfehlen. Mittels Konzentratzufütterung an ältere Mutterkuhkälber können Defizite der Lebendmasseentwicklung durch kompensatorisches Wachstum ausgeglichen und damit bei den über die Mütter schlechter versorgten Kälbern Qualitätsverbesserungen erreicht werden. Entscheidend für die Effektivität der Konzentratzufütterung ist die Höhe der Kraftfutteraufnahme, da einerseits die Kosten der Futterbereitstellung mit steigendem Verbrauch sinken und andererseits mit erhöhter Verzehrsmenge der Kraftfutteraufwand je kg Körpermassezuwachs zunimmt.The objective of this study is to show the influence of the length of the timeinterval between the calving and the taking an A.I.bull and its impact on the fertility of suckler cows as well as the fertility of suckler cows with different period of mating within a year. This study includes 901 suckler cows. With reducing the interval between calving and take an A.I.bull below 22 days the maximun number of calvings pro cow is reached. In parallel the period of calving will be delayed and the period of calving will increase. The increase of this timeinterval will lead into a more concentrated period of calving, but less calvings per cow and year. To get an average of one calving per year and cow and at the same time get a reduced and constant period of calving it is advisable to taking an A.I.bull 40 to 50 days after the calving. Within the time right before the end of the winter and right after the put out to pasture not to many cows conceive due to their bad physical conditions. Therefore, to prevent an increase of the period of calving it is advisable not to insemination of suckler cows in these timeperiods. Deficits within the rate of pregnant can be compensated in a short period of time and are therefore of less importens when choosing the suitable period of calving. Data of each 30 calfes with and without feed concentrates showed the impact the feeding concentrates of calfs of suckler cows from the calving in the wintertime during the Stallhaltungsperiode has and its influence on the development of body mass of calfes. Before the 40 day only a few calfs of suckler cows feeding concentrates. From the 70 day on the feeding of concentrates untill the put out to pasture will bring advanatges in the development of body mass. After the cessation of feeding concentrates during ranching calfes have considerable adaption problems. The calfes without feeding concentrates are capable of compensating the body mass deficiency during the period of ranching gained during the housing. The feed concentrates while the housing to calfes from the calving in the wintertime will influence the economic result of the single suckling negative if the feeding is not continuite during the ranching. 40 calfs of suckler cows originated from the calving in the sommertime have been feed with concentrates after the take back from pasture and the influence of the quantity of concentrates on the development of body mass has been gathered for each individual. The start of the feeding concentrates, the daily quantity of feed and the amount of milk differ a lot between the calfs of suckler cows because different amounts of milk provided by the suckler cows as well as the individual preference of the animals. It is advisable to limit the amount of quantity of feed because calfes with feed concentrates "eat" less basic feed and therefore luxury feeding. By concentrate feeding it is possible to compensate defizite within the development of body mass and with that have a quality improvement atwith. The most important point to have a effectiv feed concentrates is the amount of the feeding concentrates, because the costs of the delivery of feed decrease with increasing consumption and on the other hand the costs of concentrates per kg increases with increased feed

    Generation of an hiPSC-Derived Co-Culture System to Assess the Effects of Neuroinflammation on Blood-Brain Barrier Integrity

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    The blood-brain barrier (BBB) regulates the interaction between the highly vulnerable central nervous system (CNS) and the peripheral parts of the body. Disruption of the BBB has been associated with multiple neurological disorders, in which immune pathways in microglia are suggested to play a key role. Currently, many in vitro BBB model systems lack a physiologically relevant microglia component in order to address questions related to the mechanism of BBB integrity or the transport of molecules between the periphery and the CNS. To bridge this gap, we redefined a serum-free medium in order to allow for the successful co-culturing of human inducible pluripotent stem cell (hiPSC)-derived microglia and hiPSC-derived brain microvascular endothelial-like cells (BMECs) without influencing barrier properties as assessed by electrical resistance. We demonstrate that hiPSC-derived microglia exposed to lipopolysaccharide (LPS) weaken the barrier integrity, which is associated with the secretion of several cytokines relevant in neuroinflammation. Consequently, here we provide a simplistic humanised BBB model of neuroinflammation that can be further extended (e.g., by addition of other cell types in a more complex 3D architecture) and applied for mechanistic studies and therapeutic compound profiling

    Studies of Charge Exchange in a High‐Pressure Pulsed Electron Impact Source

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    This is the publisher's version, also available electronically from http://scitation.aip.org/content/aip/journal/jcp/56/3/10.1063/1.1677327.A high pressure pulsed ion source has been used in a time‐of‐flight mass spectrometer in order to study the charge exchangereactions in Ar–H2 and Ar–D2 systems using the ion source in the Čermák mode of operation. As the source was used in a pulsed mode, it was possible to identify the various secondary ions arising from the charge exchangereactions in these systems. Very good agreement has been shown to exist between the experimental results and simple theoretical deductions. Calculations have been made to determine the cross sections for the charge exchangereactions between the various species from the experimental data

    NLRP3 protects alveolar barrier integrity by an inflammasome-independent increase of epithelial cell adherence

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    Bacterial pneumonia is a major cause of acute lung injury and acute respiratory distress syndrome, characterized by alveolar barrier disruption. NLRP3 is best known for its ability to form inflammasomes and to regulate IL- 1β and IL-18 production in myeloid cells. Here we show that NLRP3 protects the integrity of the alveolar barrier in a mouse model of Streptococcus pneumoniae-induced pneumonia, and ex vivo upon treatment of isolated perfused and ventilated lungs with the purified bacterial toxin, pneumolysin. We reveal that the preserving effect of NLRP3 on the lung barrier is independent of inflammasomes, IL-1β and IL-18. NLRP3 improves the integrity of alveolar epithelial cell monolayers by enhancing cellular adherence. Collectively, our study uncovers a novel function of NLRP3 by demonstrating that it protects epithelial barrier function independently of inflammasomes

    Krueppel-Like Factor 4 Expression in Phagocytes Regulates Early Inflammatory Response and Disease Severity in Pneumococcal Pneumonia

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    The transcription factor Krueppel-like factor (KLF) 4 fosters the pro-inflammatory immune response in macrophages and polymorphonuclear neutrophils (PMNs) when stimulated with Streptococcus pneumoniae, the main causative pathogen of community-acquired pneumonia (CAP). Here, we investigated the impact of KLF4 expression in myeloid cells such as macrophages and PMNs on inflammatory response and disease severity in a pneumococcal pneumonia mouse model and in patients admitted to hospital with CAP. We found that mice with a myeloid-specific knockout of KLF4 mount an insufficient early immune response with reduced levels of pro-inflammatory cytokines and increased levels of the anti-inflammatory cytokine interleukin (IL) 10 in bronchoalveolar lavage fluid and plasma and an impaired bacterial clearance from the lungs 24 hours after infection with S. pneumoniae. This results in higher rates of bacteremia, increased lung tissue damage, more severe symptoms of infection and reduced survival. Higher KLF4 gene expression levels in the peripheral blood of patients with CAP at hospital admission correlate with a favourable clinical presentation (lower sequential organ failure assessment (SOFA) score), lower serum levels of IL-10 at admission, shorter hospital stay and lower mortality or requirement of intensive care unit treatment within 28 days after admission. Thus, KLF4 in myeloid cells such as macrophages and PMNs is an important regulator of the early proinflammatory immune response and, therefore, a potentially interesting target for therapeutic interventions in pneumococcal pneumonia

    Acute Moraxella catarrhalis Airway Infection of Chronically Smoke-Exposed Mice Increases Mechanisms of Emphysema Development : A Pilot Study

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    In chronic obstructive pulmonary disease (COPD), acute exacerbations and emphysema development are characteristics for disease pathology. COPD is complicated by infectious exacerbations with acute worsening of respiratory symptoms with Moraxella catarrhalis as one of the most frequent pathogens. Although cigarette smoke (CS) is the primary risk factor, additional molecular mechanisms for emphysema development induced by bacterial infections are incompletely understood. We investigated the impact of M. catarrhalis on emphysema development in CS exposed mice and asked whether an additional infection would induce a solubilization of pro-apoptotic and proinflammatory endothelial monocyte-activating-protein-2 (EMAPII) to exert its activities in the pulmonary microvasculature and other parts of the lungs not exposed directly to CS. Mice were exposed to smoke (6 or 9 months) and/or infected with M. catarrhalis. Lungs, bronchoalveolar lavage fluid (BALF), and plasma were analyzed. CS exposure reduced ciliated area, caused rarefaction of the lungs, and induced apoptosis. EMAPII was increased independent of prior smoke exposure in BALF of infected mice. Importantly, acute M. catarrhalis infection increased release of matrixmetalloproteases-9 and -12, which are involved in emphysema development and comprise a mechanism of EMAPII release. Our data suggest that acute M. catarrhalis infection represents an independent risk factor for emphysema development in smoke-exposed mice

    Alzheimer's Risk Gene TREM2 Determines Functional Properties of New Type of Human iPSC-Derived Microglia

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    Microglia are key in the homeostatic well-being of the brain and microglial dysfunction has been implicated in neurodegenerative disorders such as Alzheimer's disease (AD). Due to the many limitations to study microglia in situ or isolated for large scale drug discovery applications, there is a high need to develop robust and scalable human cellular models of microglia with reliable translatability to the disease. Here, we describe the generation of microglia-like cells from human induced pluripotent stem cells (iPSC) with distinct phenotypes for mechanistic studies in AD. We started out from an established differentiation protocol to generate primitive macrophage precursors mimicking the yolk sac ontogeny of microglia. Subsequently, we tested 36 differentiation conditions for the cells in monoculture where we exposed them to various combinations of media, morphogens, and extracellular matrices. The optimized protocol generated robustly ramified cells expressing key microglial markers. Bulk mRNA sequencing expression profiles revealed that compared to cells obtained in co-culture with neurons, microglia-like cells derived from a monoculture condition upregulate mRNA levels for Triggering Receptor Expressed On Myeloid Cells 2 (TREM2), which is reminiscent to the previously described disease-associated microglia. TREM2 is a risk gene for AD and an important regulator of microglia. The regulatory function of TREM2 in these cells was confirmed by comparing wild type with isogenic TREM2 knock-out iPSC microglia. The TREM2-deficient cells presented with stronger increase in free cytosolic calcium upon stimulation with ATP and ADP, as well as stronger migration towards complement C5a, compared to TREM2 expressing cells. The functional differences were associated with gene expression modulation of key regulators of microglia. In conclusion, we have established and validated a work stream to generate functional human iPSC-derived microglia-like cells by applying a directed and neuronal co-culture independent differentiation towards functional phenotypes in the context of AD. These cells can now be applied to study AD-related disease settings and to perform compound screening and testing for drug discoverySG was supported by the Roche Postdoctoral Fellowship (RPF) program and IP by the Roche Internships for Scientific Exchange (RiSE) progra
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