Modeling system states in liver cells: Survival, apoptosis and their modifications in response to viral infection

<p>Abstract</p> <p>Background</p> <p>The decision pro- or contra apoptosis is complex, involves a number of different inputs, and is central for the homeostasis of an individual cell as well as for the maintenance and regeneration of the complete organism.</p> <p>Results</p> <p>This study centers on Fas ligand (FasL)-mediated apoptosis, and a complex and internally strongly linked network is assembled around the central FasL-mediated apoptosis cascade. Different bioinformatical techniques are employed and different crosstalk possibilities including the integrin pathway are considered. This network is translated into a Boolean network (74 nodes, 108 edges). System stability is dynamically sampled and investigated using the software SQUAD. Testing a number of alternative crosstalk possibilities and networks we find that there are four stable system states, two states comprising cell survival and two states describing apoptosis by the intrinsic and the extrinsic pathways, respectively. The model is validated by comparing it to experimental data from kinetics of cytochrome c release and caspase activation in wildtype and Bid knockout cells grown on different substrates. Pathophysiological modifications such as input from cytomegalovirus proteins M36 and M45 again produces output behavior that well agrees with experimental data.</p> <p>Conclusion</p> <p>A network model for apoptosis and crosstalk in hepatocytes shows four different system states and reproduces a number of different conditions around apoptosis including effects of different growth substrates and viral infections. It produces semi-quantitative predictions on the activity of individual nodes, agreeing with experimental data. The model (SBML format) and all data are available for further predictions and development.</p

First Study of Combined Blazar Light Curves with FACT and HAWC

For studying variable sources like blazars, it is crucial to achieve unbiased monitoring, either with dedicated telescopes in pointing mode or survey instruments. At TeV energies, the High Altitude Water Cherenkov (HAWC) observatory monitors approximately two thirds of the sky every day. It uses the water Cherenkov technique, which provides an excellent duty cycle independent of weather and season. The First G-APD Cherenkov Telescope (FACT) monitors a small sample of sources with better sensitivity, using the imaging air Cherenkov technique. Thanks to its camera with silicon-based photosensors, FACT features an excellent detector performance and stability and extends its observations to times with strong moonlight, increasing the duty cycle compared to other imaging air Cherenkov telescopes. As FACT and HAWC have overlapping energy ranges, a joint study can exploit the longer daily coverage given that the observatories' locations are offset by 5.3 hours. Furthermore, the better sensitivity of FACT adds a finer resolution of features on hour-long time scales, while the continuous duty cycle of HAWC ensures evenly sampled long-term coverage. Thus, the two instruments complement each other to provide a more complete picture of blazar variability. In this presentation, the first joint study of light curves from the two instruments will be shown, correlating long-term measurements with daily sampling between air and water Cherenkov telescopes. The presented results focus on the study of the variability of the bright blazars Mrk 421 and Mrk 501 during the last two years featuring various flaring activities.Comment: 6 pages, 2 figures. Contribution to the 6th International Symposium on High Energy Gamma-Ray Astronomy (Gamma2016), Heidelberg, Germany. To be published in the AIP Conference Proceeding

Role of psychiatric hospitals during a pandemic: introducing the Munich Psychiatric COVID-19 Pandemic Contingency Plan

BACKGROUND Psychiatry is facing major challenges during the current coronavirus disease 2019 (COVID)-19 pandemic. These challenges involve its actual and perceived role within the medical system, in particular how psychiatric hospitals can maintain their core mission of attending to people with mental illness while at the same time providing relief to overstretched general medicine services. Although psychiatric disorders comprise the leading cause of the global burden of disease, mental healthcare has been deemphasised in the wake of the onslaught of the pandemic: to make room for emergency care, psychiatric wards have been downsized, clinics closed, psychiatric support systems discontinued and so on. To deal with this pressing issue, we developed a pandemic contingency plan with the aim to contain, decelerate and, preferably, avoid transmission of COVID-19 and to enable and maintain medical healthcare for patients with mental disorders. AIMS To describe our plan as an example of how a psychiatric hospital can share in providing acute care in a healthcare system facing an acute and highly infectious pandemic like COVID-19 and at the same time provide support for people with mental illness, with or without a COVID-19 infection. METHOD This was a descriptive study. RESULTS The plan was based on the German national pandemic strategy and several legal recommendations and was implemented step by step on the basis of the local COVID-19 situation. In addition, mid- and long-term plans were developed for coping with the aftermath of the pandemic. CONCLUSIONS The plan enabled the University Hospital to maintain medical healthcare for patients with mental disorders. It has offered the necessary flexibility to adapt its implementation to the first and second waves of the COVID-19 pandemic in Germany. The plan is designed to serve as an easily adaptable blueprint for psychiatric hospitals around the world

The relentless variability of Mrk 421 from the TeV to the radio

The origin of the gamma-ray emission of the blazar Mrk 421 is still a matter of debate. We used 5.5 years of unbiased observing campaign data, obtained using the FACT telescope and the Fermi LAT detector at TeV and GeV energies, the longest and densest so far, together with contemporaneous multi-wavelength observations, to characterise the variability of Mrk 421 and to constrain the underlying physical mechanisms. We studied and correlated light curves obtained by ten different instruments and found two significant results. The TeV and X-ray light curves are very well correlated with a lag of <0.6 days. The GeV and radio (15 Ghz band) light curves are widely and strongly correlated. Variations of the GeV light curve lead those in the radio. Lepto-hadronic and purely hadronic models in the frame of shock acceleration predict proton acceleration or cooling timescales that are ruled out by the short variability timescales and delays observed in Mrk 421. Instead the observations match the predictions of leptonic models.Comment: 10 pages, 8 figures, 1 tabl

Contribución al conocimiento de Porosagrotis gypaetina (Guen.) (Lep.:Noctuidae)

p.15-22Este trabajo tiene por finalidad brindar una descripcion detallada de los diferentes estados de desarrollo, asi como de los estadios larvales, de Porosagrotis gypaetina (Guen.) y estimar sus principales parametros biologicos. Se trata de una oruga conocida vulgarmente como gusano pardo que frecuenta cultivos de alfalfa, trebol bianco, maiz y girasol y determinadas malezas. Los caracteres considerados para su identificacion fueron, en el huevo: numero y distribucion de costas; en la larva: pigmentacion, distribucion de manchas y cerdas corporales; en la pupa: tamaño, forma y color y caracteristicas del cremaster; y en el adulto: ubicacion y coloracion de maculas y nervaduras alares. La emergencia de imagos alcanzo su maximo en abril y mayo. El periodo embrionario se completo en 22 a 26 dias. Aproximadamente la mitad de las larvas cumplieron su ciclo en 6 estadios y las restantes en 7; la duracion total del periodo larval fue de 134 a 141 dias, sin considerar la forma prepupal e independientemente del numero de estadios. Las orugas permanecieron como prepupas durante la temporada estival (aproximadamente 161 dias). El estado pupal duro 40 a 57 dias. Las observaciones realizadas permiten expresar que, inediante los caracteres descriptos, es factible reconocer la especie a traves no solo de los adultos, sino de sus estados inmaduros. Posee una sola generacion anual; transcurre el inviemo como larva; el daño tipico de corte lo produce a partir del cuarto estadio larval

Diagnostic reliability of the Berlin classification for complex MCA aneurysms—usability in a series of only giant aneurysms

Background and objective The main challenge of bypass surgery of complex MCA aneurysms is not the selection of the bypass type but the initial decision-making of how to exclude the affected vessel segment from circulation. To this end, we have previously proposed a classification for complex MCA aneurysms based on the preoperative angiography. The current study aimed to validate this new classification and assess its diagnostic reliability using the giant aneurysm registry as an independent data set. Methods We reviewed the pretreatment neuroimaging of 51 patients with giant (> 2.5 cm) MCA aneurysms from 18 centers, prospectively entered into the international giant aneurysm registry. We classified the aneurysms according to our previously proposed Berlin classification for complex MCA aneurysms. To test for interrater diagnostic reliability, the data set was reviewed by four independent observers. Results We were able to classify all 51 aneurysms according to the Berlin classification for complex MCA aneurysms. Eight percent of the aneurysm were classified as type 1a, 14% as type 1b, 14% as type 2a, 24% as type 2b, 33% as type 2c, and 8% as type 3. The interrater reliability was moderate with Fleiss's Kappa of 0.419. Conclusion The recently published Berlin classification for complex MCA aneurysms showed diagnostic reliability, independent of the observer when applied to the MCA aneurysms of the international giant aneurysm registry.Peer reviewe

Wirkungen des SGB II auf Personen mit Migrationshintergrund: Projekt IIa1 - 04/06 ; Jahresbericht zum 31.12.2008 - Hauptband

Auf Grundlage von Geschäftsdaten, von repräsentativen telefonischen Befragungen und von qualitativen Interviews mit Betroffenen und Fallmanagern wurden die Wirkungen der "Grundsicherung für Arbeitsuchende" auf Migrant/innen untersucht. Ihr Anteil an allen ALG-II Beziehenden beträgt im bundesweiten Durchschnitt 28 Prozent. Im Vergleich zu denjenigen ohne Migrationshintergrund sind sie im Durchschnitt jünger und haben häufiger keinen, aber auch häufiger höhere (Aus-)Bildungsabschlüsse. Die häufig fehlende Anerkennung ausländischer Abschlüsse wirkt sich auf die Arbeitsmarktchancen ebenso negativ aus wie das Fehlen jeglicher Ausbildung. Migrant/innen erhalten bei den Grundsicherungsstellen im Vergleich zu Deutschen ohne Migrationshintergrund mehr Beratungsgespräche, schließen jedoch seltener Eingliederungsvereinbarungen ab und nehmen seltener an Maßnahmen teil. Einige Herkunftsgruppen werden deutlich häufiger mit Sanktionen belegt, andere Herkunftsgruppen deutlich seltener

Long-term monitoring of bright blazars in the multi-GeV to TeV range with FACT

Blazars like Markarian 421 or Markarian 501 are active galactic nuclei (AGN), with their jets orientated towards the observer. They are among the brightest objects in the very high energy (VHE) gamma ray regime (>100 GeV). Their emitted gamma-ray fluxes are extremely variable, with changing activity levels on timescales between minutes, months, and even years. Several questions are part of the current research, such as the question of the emission regions or the engine of the AGN and the particle acceleration. A dedicated longterm monitoring program is necessary to investigate the properties of blazars in detail. A densely sampled and unbiased light curve allows for observation of both high and low states of the sources, and the combination with multi-wavelength observation could contribute to the answer of several questions mentioned above. FACT (First G-APD Cherenkov Telescope) is the first operational telescope using silicon photomultiplier (SiPM, also known as Geigermode—Avalanche Photo Diode, G-APD) as photon detectors. SiPM have a very homogenous and stable longterm performance, and allow operation even during full moon without any filter, leading to a maximal duty cycle for an Imaging Air Cherenkov Telescope (IACT). Hence, FACT is an ideal device for such a longterm monitoring of bright blazars. A small set of sources (e.g., Markarian 421, Markarian 501, 1ES 1959+650, and 1ES 2344+51.4) is currently being monitored. In this contribution, the FACT telescope and the concept of longterm monitoring of bright blazars will be introduced. The results of the monitoring program will be shown, and the advantages of densely sampled and unbiased light curves will be discussed