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The media is considered to be the fourth pillar in a democratic country. It acts as an effective control mechanism to check the other branches of the government. But this is only consequential when the media functions in an independent and transparent fashion with trained and neutral professionals who are aware of the accountability and consequences of their work. All these factors together would further the country as a democratic institution. Traditionally, it was legacy media responsible for a one-to-many communication process. Their goal was to provide information to the citizens. But this changed with development in technology and the use of social media in daily life. The internet brought with it new media formats which are easily accessible but also unstructured. These lowered barriers of entry in the media enabled citizens to become active participants in the communication process. As a result, these citizens developed a different relationship with the already existing media wherein they were not only the receivers to information but also co-producers. Real-time information allows users to communicate with each other and in turn widely generate public opinion on internet platforms. A many-to-many communication style emerged. While on the one hand, this type of discourse could be an opportunity for citizens to exercise their fundamental freedom of speech and expression, it is on the other hand, proving to have a detrimental effect in two parts: Lack of neutrality, polarized views and pre-existing misconceptions on the part of citizens as well as algorithms and formation of echo-chambers on the part of technology. Some questions arise in this scenario about the capability of citizen journalists, the duties they should adhere to along with the enjoyment of their rights and freedoms, the risks involved in an unchecked method of communication and the effect of citizen journalism in the democratic process.
Der Unfallversicherungsträger kann bei der Ausgestaltung des Beitragsausgleichsverfahrens nach § 162 Abs. 1 SGB VII die dort genannten Berechnungselemente (Zahl, Schwere oder Aufwendungen der Versicherungsfälle) alternativ oder in Kombination miteinander verwenden und eine geänderte Satzungsregelung auch auf Unfälle anwenden, deren Folgen erst im Beitragsjahr die maßgeblichen Merkmale erfüllen.
Herein we report an update to ACPYPE, a Python3 tool that now properly converts AMBER to GROMACS topologies for force fields that utilize nondefault and nonuniform 1–4 electrostatic and nonbonded scaling factors or negative dihedral force constants. Prior to this work, ACPYPE only converted AMBER topologies that used uniform, default 1–4 scaling factors and positive dihedral force constants. We demonstrate that the updated ACPYPE accurately transfers the GLYCAM06 force field from AMBER to GROMACS topology files, which employs non-uniform 1–4 scaling factors as well as negative dihedral force constants. Validation was performed using β-d-GlcNAc through gas-phase analysis of dihedral energy curves and probability density functions. The updated ACPYPE retains all of its original functionality, but now allows the simulation of complex glycomolecular systems in GROMACS using AMBER-originated force fields. ACPYPE is available for download at https://github.com/alanwilter/acpype.
Ereignet sich ein Unfall auf dem Heimweg vom Arbeitsplatz, während die betroffene Arbeitnehmerin mit einem Mobiltelefon telefoniert (sogenannte „gemischte Tätigkeit“), so scheidet ein Wegeunfall dann aus, wenn die Unfallentstehung überwiegend dem Telefonieren zuzurechnen ist und dieses damit für die Unfallentstehung wesentlich war.
Treatment options for acute myeloid leukemia (AML) remain extremely limited and associated with significant toxicity. Nicotinamide phosphoribosyltransferase (NAMPT) is involved in the generation of NAD+ and a potential therapeutic target in AML. We evaluated the effect of KPT-9274, a p21-activated kinase 4/NAMPT inhibitor that possesses a unique NAMPT-binding profile based on in silico modeling compared with earlier compounds pursued against this target. KPT-9274 elicited loss of mitochondrial respiration and glycolysis and induced apoptosis in AML subtypes independent of mutations and genomic abnormalities. These actions occurred mainly through the depletion of NAD+, whereas genetic knockdown of p21-activated kinase 4 did not induce cytotoxicity in AML cell lines or influence the cytotoxic effect of KPT-9274. KPT-9274 exposure reduced colony formation, increased blast differentiation, and diminished the frequency of leukemia-initiating cells from primary AML samples; KPT-9274 was minimally cytotoxic toward normal hematopoietic or immune cells. In addition, KPT-9274 improved overall survival in vivo in 2 different mouse models of AML and reduced tumor development in a patient-derived xenograft model of AML. Overall, KPT-9274 exhibited broad preclinical activity across a variety of AML subtypes and warrants further investigation as a potential therapeutic agent for AML.
Survival of patients with pediatric acute lymphoblastic leukemia (ALL) after allogeneic hematopoietic stem cell transplantation (allo-SCT) is mainly compromised by leukemia relapse, carrying dismal prognosis. As novel individualized therapeutic approaches are urgently needed, we performed whole-exome sequencing of leukemic blasts of 10 children with post–allo-SCT relapses with the aim of thoroughly characterizing the mutational landscape and identifying druggable mutations. We found that post–allo-SCT ALL relapses display highly diverse and mostly patient-individual genetic lesions. Moreover, mutational cluster analysis showed substantial clonal dynamics during leukemia progression from initial diagnosis to relapse after allo-SCT. Only very few alterations stayed constant over time. This dynamic clonality was exemplified by the detection of thiopurine resistance-mediating mutations in the nucleotidase NT5C2 in 3 patients’ first relapses, which disappeared in the post–allo-SCT relapses on relief of selective pressure of maintenance chemotherapy. Moreover, we identified TP53 mutations in 4 of 10 patients after allo-SCT, reflecting acquired chemoresistance associated with selective pressure of prior antineoplastic treatment. Finally, in 9 of 10 children’s post–allo-SCT relapse, we found alterations in genes for which targeted therapies with novel agents are readily available. We could show efficient targeting of leukemic blasts by APR-246 in 2 patients carrying TP53 mutations. Our findings shed light on the genetic basis of post–allo-SCT relapse and may pave the way for unraveling novel therapeutic strategies in this challenging situation.
Lässt sich das erforderliche zeitlich begrenzte, von außen auf den Körper einwirkende Ereignis nicht im Vollbeweis sichern, fehlt es an der erforderlichen haftungsbegründenden Kausalität – mit der Folge, dass das geltend gemachte Unfallereignis nicht als Arbeitsunfall anzuerkennen ist. Bleibt unklar, welche Handlungen der Versicherte zum Zeitpunkt des Unfallereignisses vorgenommen hat, sind auch die Grundsätze des so genannten Anscheinsbeweises unanwendbar, weil ein typischer Geschehensablauf nicht nachweisbar ist.
Erfassung der N-Dynamik verschiedener Wirtschaftsdünger in Wintergerste und Senf im Dürrejahr 2018
(2019)
Eine Organisationspflichtverletzung des Arbeitgebers, aus der keine gesundheitsschädigende Einwirkung beim Versicherten resultiert, sondern nur eine Nothilfemaßnahme für eine berufsunabhängige Gesundheitsstörung unterbleibt, erfüllt insoweit nicht die Voraussetzungen eines Arbeitsunfalls. Das Fehlen eines Defibrillators an der Betriebsstätte begründet schon kein Organisationsverschulden des Arbeitgebers, denn die Vorhaltung eines Defibrillators zur Anwendung durch Laien ist nicht verpflichtend gesetzlich geregelt.
Die Herausforderungen an die gesetzliche Rentenversicherung in Folge des Wandels in der Arbeitswelt
(2019)
Abläufe wie Schieben, Gegenstemmen, Heben, Tragen, Sprung aus der Hocke sind nicht willkürlich gesteuerte Belastungen der Sehne und damit als Gelegenheitsanlässe und nicht Unfallereignisse anzusehen. Entsprechende Abläufe können die Sehne nicht gefährden, es fehlt hierbei bereits an der physiologisch-naturwissenschaftlichen Kausalität.
Political Impact Management
(2019)
Humankind, it can be argued, lives beyond its means and often at the expense of future generations. This paper starkly demonstrates, with the aid of a mathematical model, the imperative for a sustainable existence. In the model, consumption of resources is represented as a closed system, just like our planet. Long-term survival is only possible if consumption is below the ability of the system to regenerate.